Journal articles: 'IVDR'

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Nayak, Shashank, M. P. Venkatesh, and Pramod Kumar T.M. "EU IVDR Regulatory Changes: An Overview of Requirements in (EU) 2017/746." Applied Clinical Research, Clinical Trials and Regulatory Affairs 7, no. 3 (December 24, 2020): 237–43. http://dx.doi.org/10.2174/2213476x07666200327143023.

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IVDR is the new regulatory basis for placing IVDs in the market, making them available and putting them into service in the European market. EU IVDR regulation is much bigger than the impact of EU IVDD, which is a bold statement to make, considering the significant industry- wide impact as it presents challenges to the manufacturer. Rather, it is largely a revision that contains guidance on how to fulfill the existing IVDD requirements. IVDR focused on the IVD-specific provisions therein regarding classification, performance evaluations, clinical data, conformity assessments and notified bodies. IVDR presents enormous change to the IVD industry, not only because it needs a significant change in technical documentation and Quality management system, but also because it changes the relationship with the economic operator and their responsibilities.

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Du, Zhenya, Fusheng Chen, Kunlun Liu, Shaojuan Lai, Lifen Zhang, Guanhao Bu, Xueli Gao, and Shaobo Liu. "Effects of Extruded Soy Protein on the Quality of Chinese Steamed Bread." Journal of Chemistry 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/3691523.

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Five different extruded soy protein isolates (ESPIs) were obtained by extrusion and denoted by IVD1, IVD2, IVD3, IVD4, and IVD5. Then the SDS-PAGE results showed that the subunits of SPI decreased after extrusion, especially the subunits of 90.8, 32.8, and 31.3 kDa, whereas no isopeptide bond was formed. Although SPI improved both the development time (DT) and stability (S) of dough, ESPIs increasedSbut the DT decreased from 4.3 min to 1.8–2.0 min. Texture profile analysis (TPA) results showed that the hardness and chewiness of Chinese steamed bread (CSB) decreased in the order wheat flour+IVD2 (WF+IVD2), WF+SPI, WF+IVD4, WF+IVD1, WF+IVD3, WF, and WF+IVD5. As regards color, the total colorΔEdecreased except for the WF+IVD1 (56.22); its positive and negative trends ofL⁎andb⁎were invariant with the SPI or ESPIs mixture, whereasa⁎showed a positive trend. The sensory score increased from 82.7 to 83.4 with 3% of SPI addition and up to 87.8 when the substitution was IVD1. Therefore, SPI treated by extrusion may significantly improve the quality of CSB.

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Naga Gouri T, Venkatesh M P, Balamuralidhara V, and Pramod Kumar T M. "A futuristic study on in-vitro medical devices regulations." International Journal of Research in Pharmaceutical Sciences 11, no. 2 (April 28, 2020): 2221–27. http://dx.doi.org/10.26452/ijrps.v11i2.2173.

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The In-Vitro Medical Devices Directive (IVDD) established in 1998 by the European Union met the requirements of the single medical device market. In the due course, IVDD could not regulate all new technical and medical developments in the sector. The IVDD 98/79/EC, was preceded with IVDR 2017//746; which defined and demonstrated conformity to essential requirements, established harmonized standards and facilitated the organization of ‘Notified Body’ (NB), Competent Authority oversight and market surveillance. IVDR implemented streamlines as defined in Annex I of the EU IVDR 2017/746 conforming to the relationships between the performance requirements and general safety, and Annex I of the EU Directive 98/79/EC for IVDD for the essential requirements. The importance of the Unique Device Identification and its implementation in the safety and conformity of the device was made stringent for the manufacturers. The recent developments in IVDR, with reference to EUDAMED database, enable the applicant for accessing of data entered for the revival, correction and the assessing of information.

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Vermeersch, Pieter, Tobias Van Aelst, and Elisabeth M. C. Dequeker. "The new IVD Regulation 2017/746: a case study at a large university hospital laboratory in Belgium demonstrates the need for clarification on the degrees of freedom laboratories have to use lab-developed tests to improve patient care." Clinical Chemistry and Laboratory Medicine (CCLM) 59, no. 1 (January 26, 2021): 101–6. http://dx.doi.org/10.1515/cclm-2020-0804.

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AbstractObjectivesThe new European In Vitro Diagnostic (IVD) Regulation 2017/746 (IVDR) restricts the use of lab-developed tests (LDT) after 26th May 2022. There are no data on the impact of the IVDR on laboratories in the European Union.MethodsLaboratory tests performed in UZ Leuven were divided in four groups: core laboratory, immunology, special chemistry, and molecular microbiology testing. Each test was classified as Conformité Européenne (CE)-IVD, modified/off-label CE-IVD, commercial Research Use Only (RUO) or LDT. Each matrix was considered a separate test.ResultsWe found that 97.6% of the more than 11.5 million results/year were generated with a CE-IVD method. Of the 922 different laboratory tests, however, only 41.8% were CE-IVD, 10.8% modified/off-label CE-IVD, 0.3% RUO, and 47.1% LDT. Off-label CE-IVD was mainly used to test alternative matrices not covered by the claim of the manufacturer (e.g., pleural or peritoneal fluid). LDTs were mainly used for special chemistry, flow cytometry, and molecular testing. Excluding flow cytometry, the main reasons for the use of 377 LDTs were lack of a CE-IVD method (71.9%), analytical requirements (14.3%), and the fact the LDT was in use before CE-IVD available (11.9%).ConclusionsWhile the large majority of results (97.6%) were generated with a CE-IVD method, only 41.8% of laboratory tests were CE-IVD. There is currently no alternative on the market for 71.5% of the 537 LDTs performed in our laboratory which do not fall within the scope of the current IVD directive (IVDD). Compliance with the IVDR will require a major investment of time and effort.

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Jacobs, Leo. "IVDR." Laboratoriumgeneeskunde 3, no. 5 (October 2020): 6. http://dx.doi.org/10.24078/labgeneeskunde.2020.10.126050.

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Kugiya, F., H. Nishida, A. Saitou, and N. Kodama. "iVDR business perspective." Journal of Magnetism and Magnetic Materials 320, no. 22 (November 2008): 2894–99. http://dx.doi.org/10.1016/j.jmmm.2008.07.043.

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Tawfik, O., L. Peterson, R. Parker, E. Mechetner, M. Davis, J. Chapman, Q. Khan, and J. Ma. "Correlation between immunohistochemical biomarker expression and in vitro drug response factors in stage III-IV ovarian cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 16055. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.16055.

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16055 Background: The reliability of molecular biomarkers as predictors of treatment outcome remains unclear and, in relation to drug resistance even less is known. Immunohistochemical (IHC) expression of biomarkers and in vitro drug resistance (IVDR) relative to clinical outcome were evaluated in patients with stage III-IV epithelial ovarian cancer (OC) who received combination carboplatin (CAR) plus paclitaxel (TAX) chemotherapy. Methods: We correlated clinical outcome with histopathology and biomarker expression of MIB-1, p53, BCL2, EGFR, ER and PR in 98 OC patients with tumors tested for IVDR by extreme drug resistance (EDR) assay. IVDR was determined following exposures to single agents CAR, cisplatin (CP), TAX, taxotere (TXT), gemcitabine (GCB), topotecan (TP), liposomil doxorubicin, and cytoxan (CT). Percentage cell growth inhibition (PCI) for each drug was compared with PCI from untreated control cultures. Results: Tumors with prior chemotherapy (n=29) were more resistant to CAR (unpaired t-test, p=0.046), and CT (p=0.038), and more sensitive to liposomil doxorubicin (p=0.009), compared to treatment naive tumors (n=53). For 65 tumors, there was a positive relationship between MIB-1 vs p53 (r=0.419; p=0.001), and between ER vs PR (r=0.339; p=0.011). Correlation between biomarkers and drug response showed a significantly inverse relationship between MIB-1 vs liposomil doxorubicin, p53 vs liposomil doxorubicin, EGFR vs CAR, CP, GCB and TAX; and between ER vs TXT and CT, and PR vs CT and TP. With a 53% (33/61) response rate to CAR+TAX, time to progression (TTP) for responders (R) with EGFR+ tumors was longer (median TTP 15.6 mo); and shorter for R with EGFR- tumors (p=0.008). For R and non-R, BCL2+ tumors had longer overall survival (OS) (median OS 23.3 mo; p=0.006). No other significant correlations were seen. Conclusion: Prior chemotherapy increased IVDR to CAR and CT, and increased sensitivity to liposomil doxorubicin. Increased expression of proliferation biomarkers, particularly EGFR, correlated with resistance to several chemotherapeutic agents. EGFR expression in responders was associated with longer TTP. The significance of in vitro correlates of prognostic biomarker expression and IVDR for predicting chemoresistance warrants prospective studies to assess its value in clinical settings. [Table: see text]

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De Decker, Steven, Anne-Sophie Warner, and Holger A. Volk. "Prevalence and breed predisposition for thoracolumbar intervertebral disc disease in cats." Journal of Feline Medicine and Surgery 19, no. 4 (July 9, 2016): 419–23. http://dx.doi.org/10.1177/1098612x16630358.

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Objectives The objective was to evaluate the prevalence and possible breed predilections for thoracolumbar intervertebral disc disease (IVDD) in cats. Methods Medical records and imaging studies of cats diagnosed with thoracolumbar IVDD between January 2008 and August 2014 were retrospectively reviewed and compared with the general hospital population. The association between type of IVDD (ie, intervertebral disc extrusion [IVDE] or intervertebral disc protrusion [IVDP]) and breed, age, sex, and duration and severity of clinical signs was also evaluated. Results Of 12,900 cats presented during the study period, 31 (0.24%) were diagnosed with IVDD, including 17 purebred and 14 non-purebred cats. Of all presented purebred cats, 0.52% were diagnosed with thoracolumbar IVDD. More specifically, 1.29% of all British Shorthairs and 1.83% of all presented Persians were diagnosed with IVDD. Compared with the general hospital population, purebred cats ( P = 0.0001), British Shorthairs ( P <0.0001) and Persians ( P = 0.0006) were significantly overrepresented with thoracolumbar IVDD. Affected purebred cats were younger than affected non-purebred cats ( P = 0.02). Of 31 cats with IVDD, 19 were diagnosed with IVDE and 12 with IVDP. Cats with IVDE had a significantly shorter duration of clinical signs ( P = 0.0002) and demonstrated more severe neurological deficits ( P = 0.04) than cats with IVDP. Conclusions and relevance Although thoracolumbar IVDD is an uncommon condition in cats, purebred cats, British Shorthairs and Persians, were overrepresented. It is currently unclear if this represents a true breed predisposition or a higher likelihood of owners of purebred cats seeking referral for advanced diagnostic imaging procedures.

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Kupka, Johannes, Annika Kohler, Karima El Bagdadi, Richard Bostelmann, Marco Brenneis, Christoph Fleege, Danny Chan, et al. "Adrenoceptor Expression during Intervertebral Disc Degeneration." International Journal of Molecular Sciences 21, no. 6 (March 18, 2020): 2085. http://dx.doi.org/10.3390/ijms21062085.

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Healthy and degenerating intervertebral discs (IVDs) are innervated by sympathetic nerves, however, adrenoceptor (AR) expression and functionality have never been investigated systematically. Therefore, AR gene expression was analyzed in both tissue and isolated cells from degenerated human IVDs. Furthermore, human IVD samples and spine sections of wildtype mice (WT) and of a mouse line that develops spontaneous IVD degeneration (IVDD, in SM/J mice) were stained for ARs and extracellular matrix (ECM) components. In IVD homogenates and cells α1a-, α1b-, α2a-, α2b-, α2c-, β1-, and β2-AR genes were expressed. In human sections, β2-AR was detectable, and its localization parallels with ECM alterations. Similarly, in IVDs of WT mice, only β2-AR was expressed, and in IVDs of SM/J mice, β2AR expression was stronger accompanied by increased collagen II, collagen XII, decorin as well as decreased cartilage oligomeric matrix protein expression. In addition, norepinephrine stimulation of isolated human IVD cells induced intracellular signaling via ERK1/2 and PKA. For the first time, the existence and functionality of ARs were demonstrated in IVD tissue samples, suggesting that the sympathicus might play a role in IVDD. Further studies will address relevant cellular mechanisms and thereby help to develop novel therapeutic options for IVDD.

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SAITOU, Atsushi, Fumio KUGIYA, and Naoki KODAMA. "Standardization ^|^amp; Application Expansion Activity of Removable HDD (iVDR)." IEICE Transactions on Electronics E96.C, no. 12 (2013): 1508–14. http://dx.doi.org/10.1587/transele.e96.c.1508.

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Becht, Christine, and Thomas Willaschek. "In-vitro-Diagnostika aus Eigenherstellung unter Geltung der IVDR." Medizinrecht 39, no. 9 (September 2021): 809–13. http://dx.doi.org/10.1007/s00350-021-5978-8.

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Schnell-Inderst, Petra, and Claudia Wild. "PP32 Joint Early Dialogs Between Medical Device Regulation and Health Technology Assessment." International Journal of Technology Assessment in Health Care 35, S1 (2019): 43. http://dx.doi.org/10.1017/s026646231900196x.

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IntroductionIn Europe, the new Medical Device Regulation (MDR) and In Vitro Diagnostics Regulation (IVDR) that entered into force 2017 will have to be applied until 2020 and 2022, respectively. Under the old regulation, there was a large gap between evidence requirements for market approval and market access for high risk (class IIb and III) medical devices (MD). The MDR/IVDR will require appropriate clinical investigations for these MD classes. Despite the different purpose of market approval and surveillance and reimbursement decisions, there are possible synergies with regard to evidence generation, for example, design of pivotal trials and post-launch evidence generation with observational data. In the MDR, early scientific advice can be provided by expert panels of the European Commission if requested by MD developers. For medicinal products, the European network for Health Technology Assessment (EUnetHTA) has established joint early dialogs (JED) of HTA agencies with the European Medicines Agency and manufacturers. A similar approach might be possible with the Medical Device Coordination Group (MDCG). The objective was to explore possible synergies for JED with the MDCG and EUnetHTA.MethodsIn 2018, EUnetHTA established a task force for HTA and MDR/IVDR. A workshop, which will explore possible synergies and activities on JED as well as the viewpoints of stakeholders will be held in May 2019. Participants will be Directorate-Generals GROW (Internal Market, Industry, Entrepreneurship and SME) and SANTE (Health and Food Safety), EUnetHTA members assessing MD, representatives of national competent authorities, Team Notified Bodies, MedTech Europe, patient representatives and academia.ResultsA report on the presentations, the results of the discussion, and next steps in a possible collaboration will be presented.ConclusionsJoint early scientific advice to manufacturers on the European level for evidence generation by HTA agencies and the MDCG has the potential to streamline evidence generation in the life cycle of high risk MD.

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Kahveci, R., and P. Usakpinar. "PMD138 - IMPACTS OF NEW EU MDR&IVDR REGULATIONS FOR TURKEY." Value in Health 21 (October 2018): S266—S267. http://dx.doi.org/10.1016/j.jval.2018.09.1587.

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Vogeser, Michael. "IVDR and diagnostic application of mass spectrometry in the European Union." Journal of Mass Spectrometry and Advances in the Clinical Lab 19 (January 2021): 32–33. http://dx.doi.org/10.1016/j.jmsacl.2021.02.001.

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Oh, Jae-Young, Jun-Geon Je, Hyo-Geun Lee, Eun-A. Kim, Sang In Kang, Jung-Suck Lee, and You-Jin Jeon. "Anti-Hypertensive Activity of Novel Peptides Identified from Olive Flounder (Paralichthys olivaceus) Surimi." Foods 9, no. 5 (May 18, 2020): 647. http://dx.doi.org/10.3390/foods9050647.

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There is a growing interest in the health benefits of functional foods. A benefit that has been long sought is the control of hypertension through dietary approaches. Hypertension has been implicated as a risk factor for cardiovascular disease and is therefore of clinical significance. Here, we aim to demonstrate the antihypertensive activity of novel peptides derived from surimi, a functional food ingredient made from refined fish myofibrillar proteins. Three peptides, Ile-Val-Asp-Arg (IVDR), Trp-Tyr-Lys (WYK), and Val-Ala-Ser-Val-Ile (VASVI), were isolated from surimi made from the olive flounder (Paralichthys olivaceus). Our results show that IVDR, WYK, and VASVI exhibited high Angiotensin I-converting Enzyme (ACE) inhibition activity. These peptides are also shown to increase phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS), and significantly promote nitric oxide (NO) production in human umbilical vein endothelial cells. Oral administration of the peptides decreased blood pressure in spontaneously hypertensive rats (SHRs), thereby confirming that the peptides derived from surimi perform antihypertensive activity via the Akt/eNOS pathway. These results indicate that surimi made from P. olivaceus contains novel antihypertensive peptides that could be used to enhance the health benefits of food ingredients.

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Heinzelmann, Elsbeth. "The New, Stringent MDR and IVDR Regulations: Viewing this Change as an Opportunity." CHIMIA International Journal for Chemistry 72, no. 6 (June 27, 2018): 430–31. http://dx.doi.org/10.2533/chimia.2018.430.

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Bossuyt, P. "What type of clinical evidence study designs are required in the new IVDR era?" Clinica Chimica Acta 493 (June 2019): S750. http://dx.doi.org/10.1016/j.cca.2019.03.1465.

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Barberis, Massimo. "In vitro diagnostic medical device regulation (IVDR): the end of laboratory developed tests (LDT)?" Pathologica 113, no. 2 (April 2021): 68–69. http://dx.doi.org/10.32074/1591-951x-237.

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Lin, Yazhou, Guoqing Tang, Yucheng Jiao, Ye Yuan, Yuehuan Zheng, Yong Chen, Jiaqi Xiao, Changwei Li, Zhe Chen, and Peng Cao. "Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-κB Pathway." Oxidative Medicine and Cellular Longevity 2018 (August 19, 2018): 1–12. http://dx.doi.org/10.1155/2018/3692752.

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Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2 expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2 expressions via a reactive oxygen species- (ROS-) dependent NF-κB cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE2 expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-κB pathway is likely responsible for the pathology of IVDD.

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Yan, Zhengjian, Liangjun Yin, Zhongliang Wang, Jixing Ye, Zhonglin Zhang, Ruifang Li, Sahitya K. Denduluri, et al. "A Novel Organ Culture Model of Mouse Intervertebral Disc Tissues." Cells Tissues Organs 201, no. 1 (October 9, 2015): 38–50. http://dx.doi.org/10.1159/000439268.

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The intervertebral disc (IVD) is a fibrocartilaginous joint between two vertebral bodies. An IVD unit consists of a gelatinous central nucleus pulposus, encased by the annulus fibrosus, which is sandwiched between cartilaginous endplates (EPs). The IVD homeostasis can be disrupted by injuries, ageing and/or genetic predispositions, leading to degenerative disc disorders and subsequent lower back pain. The complex structure and distinct characteristics of IVDs warrant the establishment of robust in vitro IVD organ culture for studying the etiology and treatment of disc degeneration. Here, we isolate mouse lumbar IVDs and culture the minimal IVD units in submersion or suspension medium supplemented with 2% bovine serum or 10% fetal bovine serum (FBS). We find the minimal IVD units remain healthy for up to 14 days when cultured in submersion culture supplemented with 10% FBS. New bone formation in the EPs of the cultured IVDs can be assessed with calcein labeling. Furthermore, the cultured IVDs can be effectively transduced by recombinant adenovirus, and transgene expression lasts for 2 weeks. Thus, our findings demonstrate that the optimized IVD organ culture system can be used to study IVD biology and screen for biological factors that may prevent, alleviate and/or treat disc degeneration.

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Du, Yuxiang, Zhikun Wang, Yangming Wu, Chengyi Liu, and Lingli Zhang. "Intervertebral Disc Stem/Progenitor Cells: A Promising “Seed” for Intervertebral Disc Regeneration." Stem Cells International 2021 (July 28, 2021): 1–12. http://dx.doi.org/10.1155/2021/2130727.

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Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain (LBP), which has become more prevalent from 21 century, causing an enormous economic burden for society. However, in spite of remarkable improvements in the basic research of IVD degeneration (IVDD), the effects of clinical treatments of IVDD are still leaving much to be desired. Accumulating evidence has proposed the existence of endogenous stem/progenitor cells in the IVD that possess the ability of proliferation and differentiation. However, few studies have reported the biological properties and potential application of IVD progenitor cells in detail. Even so, these stem/progenitor cells have been consumed as a promising cell source for the regeneration of damaged IVD. In this review, we will first introduce IVD, describe its physiology and stem/progenitor cell niche, and characterize IVDSPCs between homeostasis and IVD degeneration. We will then summarize recent studies on endogenous IVDSPC-based IVD regeneration and exogenous cell-based therapy for IVDD. Finally, we will discuss the potential applications and future developments of IVDSPC-based repair of IVD degeneration.

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Frenken, Miriam, Sven Nebelung, Christoph Schleich, Anja Müller-Lutz, Karl Ludger Radke, Benedikt Kamp, Matthias Boschheidgen, et al. "Non-Specific Low Back Pain and Lumbar Radiculopathy: Comparison of Morphologic and Compositional MRI as Assessed by gagCEST Imaging at 3T." Diagnostics 11, no. 3 (February 26, 2021): 402. http://dx.doi.org/10.3390/diagnostics11030402.

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Using glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) magnetic resonance imaging (MRI), this study comparatively evaluated the GAG contents of lumbar intervertebral disks (IVDs) of patients with non-specific low back pain (nsLBP), radiculopathy, and asymptomatic volunteers to elucidate the association of clinical manifestation and compositional correlate. A total of 18 patients (mean age 57.5 ± 22.5 years) with radiculopathy, 16 age-matched patients with chronic nsLBP and 20 age-matched volunteers underwent standard morphologic and compositional gagCEST MRI on a 3T scanner. In all cohorts, GAG contents of lumbar IVDs were determined using gagCEST MRI. An assessment of morphologic IVD degeneration based on the Pfirrmann classification and T2-weighted sequences served as a reference. A linear mixed model adjusted for multiple confounders was used for statistical evaluation. IVDs of patients with nsLBP showed lower gagCEST values than those of volunteers (nsLBP: 1.3% [99% confidence intervals (CI): 1.0; 1.6] vs. volunteers: 1.9% [99% CI: 1.6; 2.2]). Yet, IVDs of patients with radiculopathy (1.8% [99% CI: 1.4; 2.1]) were not different from patients with nsLBP or volunteers. In patients with radiculopathy, IVDs directly adjacent to IVD extrusions demonstrated lower gagCEST values than distant IVDs (adjacent: 0.9% [99% CI: 0.3; 1.5], distant: 2.1% [99% CI: 1.7; 2.5]). Advanced GAG depletion in nsLBP and directly adjacent to IVD extrusions in radiculopathy indicates close interrelatedness of clinical pathology and compositional degeneration.

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Ishikawa, Tetsuhiro, Atsuya Watanabe, Hiroto Kamoda, Masayuki Miyagi, Gen Inoue, Kazuhisa Takahashi, and Seiji Ohtori. "Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model." Asian Spine Journal 12, no. 2 (April 30, 2018): 317–24. http://dx.doi.org/10.4184/asj.2018.12.2.317.

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<sec><title>Study Design</title>An <italic>in vivo</italic> histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted.</sec><sec><title>Purpose</title>To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated.</sec><sec><title>Overview of Literature</title>The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content.</sec><sec><title>Methods</title>Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining.</sec><sec><title>Results</title>Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs (<italic>p</italic><0.05). There was a significant difference between grade 1 and grade 2 IVDs only in terms of T1ρ values (<italic>p</italic><0.05).</sec><sec><title>Conclusions</title>T1ρ and T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.</sec>

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Krut, Zoe, Gadi Pelled, Dan Gazit, and Zulma Gazit. "Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration." Cells 10, no. 9 (August 29, 2021): 2241. http://dx.doi.org/10.3390/cells10092241.

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Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance of the anabolic and catabolic processes in the intervertebral disc, leading to an alteration in the composition of the extracellular matrix (ECM), loss of nucleus pulposus (NP) cells, excessive oxidative stress and inflammation. Degeneration of the IVD occurs naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression. IVDD, often referred to as degenerative disc disease (DDD), poses an increasingly substantial financial burden due to the aging population and increasing incidence of obesity in the United States. Current treatments for IVDD include pharmacological and surgical interventions, but these lack the ability to stop the progression of disease and restore the functionality of the IVD. Biological therapies have been evaluated but show varying degrees of efficacy in reversing disc degeneration long-term. Stem cell-based therapies have shown promising results in the regeneration of the IVD, but face both biological and ethical limitations. Exosomes play an important role in intercellular communication, and stem cell-derived exosomes have been shown to maintain the therapeutic benefit of their origin cells without the associated risks. This review highlights the current state of research on the use of stem-cell derived exosomes in the treatment of IVDD.

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Kato, K., K. Akeda, S. Miyazaki, J. Yamada, C. Muehleman, K. Miyamoto, YA Asanuma, et al. "NF-kB decoy oligodeoxynucleotide preserves disc height in a rabbit anular-puncture model and reduces pain induction in a rat xenograft-radiculopathy model." European Cells and Materials 42 (July 20, 2021): 90–109. http://dx.doi.org/10.22203/ecm.v042a07.

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While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes’ expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-κB decoy is an oligodeoxynucleotide containing the NF-κB binding site that entraps NF-κB subunits, resulting in suppression of NF-κB activity. In the present preclinical study, NF-κB decoy was injected into degenerated IVDs using the rabbit anular-puncture model. In terms of distribution, NF-κB decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-κB decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-κB decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-κB decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-α, in rabbit degenerated IVDs. NF-κB decoy also reduced the pain response as seen using the “pain sensor” nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-κB decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-κB decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs.

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Mahmoud, Mohamed, Maria Kokozidou, Alexander Auffarth, and Gundula Schulze-Tanzil. "The Relationship between Diabetes Mellitus Type II and Intervertebral Disc Degeneration in Diabetic Rodent Models: A Systematic and Comprehensive Review." Cells 9, no. 10 (September 29, 2020): 2208. http://dx.doi.org/10.3390/cells9102208.

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The number of diabetic patients grows constantly worldwide. Many patients suffer simultaneously from diabetes mellitus type 2 (T2DM) and intervertebral disc disease (IVDD), suggesting a strong link between T2DM and IVDD. T2DM rodent models provide versatile tools to study this interrelation. We hypothesized that the previously achieved studies in rodents approved it. Performing a search in the publicly available electronic databases according to our inclusion (e.g., experimental study with clearly outlined methods investigating IVDD in diabetic rodent models) and exclusion (e.g., non-experimental) criteria, we included 23 studies from 1992 to 2020 analyzing different aspects of IVDD in diabetic rodents, such as on pathogenesis (e.g., effects of hyperglycemia on IVD cells, sirtuin (SIRT)1/p53 axis in the interrelation between T2DM and IVDD), risk factors (e.g., high content of advanced glycation end-products (AGEs) in modern diets), therapeutical approaches (e.g., insulin-like growth factor (IGF-I)), and prophylaxis. Regarding their quality, 12 studies were classified as high, six as moderate, and five as low. One strong, 18 moderate, and three mild evidences of the link between DM and IVDD in rodents were found, while only one study has not approved this link. We concluded that T2DM has a devastating effect on IVD, particularly in advanced cases, which needs to be further evaluated.

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Belavy, Daniel L., Helena Brisby, Benjamin Douglas, Hanna Hebelka, Matthew J. Quittner, Patrick J. Owen, Timo Rantalainen, Guy Trudel, and Kerstin M. Lagerstrand. "Characterization of Intervertebral Disc Changes in Asymptomatic Individuals with Distinct Physical Activity Histories Using Three Different Quantitative MRI Techniques." Journal of Clinical Medicine 9, no. 6 (June 12, 2020): 1841. http://dx.doi.org/10.3390/jcm9061841.

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(1) Background: Assessments of intervertebral disc (IVD) changes, and IVD tissue adaptations due to physical activity, for example, remains challenging. Newer magnetic resonance imaging techniques can quantify detailed features of the IVD, where T2-mapping and T2-weighted (T2w) and Dixon imaging are potential candidates. Yet, their relative utility has not been examined. The performances of these techniques were investigated to characterize IVD differences in asymptomatic individuals with distinct physical activity histories. (2) Methods: In total, 101 participants (54 women) aged 25–35 years with distinct physical activity histories but without histories of spinal disease were included. T11/12 to L5/S1 IVDs were examined with sagittal T2-mapping, T2w and Dixon imaging. (3) Results: T2-mapping differentiated Pfirrmann grade-1 from all other grades (p < 0.001). Most importantly, T2-mapping was able to characterize IVD differences in individuals with different training histories (p < 0.005). Dixon displayed weak correlations with the Pfirrmann scale, but presented significantly higher water content in the IVDs of the long-distance runners (p < 0.005). (4) Conclusions: Findings suggested that T2-mapping best reflects IVD differences in asymptomatic individuals with distinct physical activity histories changes. Dixon characterized new aspects of IVD, probably associated with IVD hypertrophy. This complementary information may help us to better understand the biological function of the disc.

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He, Mingwei, Jinlei Pang, Haiyan Sun, Guanrong Zheng, Yan Lin, and Weipeng Ge. "P14ARF inhibits regional inflammation and vascularization in intervertebral disc degeneration by upregulating TIMP3." American Journal of Physiology-Cell Physiology 318, no. 4 (April 1, 2020): C751—C761. http://dx.doi.org/10.1152/ajpcell.00271.2019.

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In this study, we identified P14 alternate reading frame (P14ARF) as a novel regulator of inflammation and vascularization in intervertebral disk degeneration (IVDD). We collected IVD tissues from IVDD patients and normal individuals for analysis of P14ARF expression. We also induced experimental IVDD by needle puncture injuries in the caudal intervertebral disks of Sprague-Dawley (SD) rats and achieved recombinant adenovirus-mediated P14ARF overexpression in experimental IVDD rats. Regulation relationships between P14ARF and tissue inhibitors of metalloproteinases-3 (TIMP3) were confirmed in P14ARF-overexpressed and TIMP3-depleted nucleus pulposus (NP) cells. Tube formation in vitro was evaluated in coculture systems of human umbilical vein endothelial cells (HUVECs) and rat degenerated NP cells (DNPCs). Inflammatory response was assessed from levels of TNF-α, IL-1β, and IL-6 and neovascularization from expression of endothelial growth factor (VEGF). The P14ARF and TIMP3 were downregulated in degenerated IVD tissue derived from patients and experimental IVDD rats. Overexpressed P14ARF suppressed inflammatory cytokine levels and vascularization. There was decreased in vitro tube formation in response to P14ARF overexpression and TIMP3 elevation. Finally, attenuated inflammatory responses and suppression of VEGF were achieved by P14ARF-mediated promotion of TIMP3 in rat DNPCs. Taken together, the present study reveals that P14ARF/TIMP3 modulation of inflammatory response and vascularization in the context of IVDD highlights a potential target for future therapeutic strategies.

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Huang, Zhao, Benjamin Kohl, Maria Kokozidou, Stephan Arens, and Gundula Schulze-Tanzil. "Establishment of a Cytocompatible Cell-Free Intervertebral Disc Matrix for Chondrogenesis with Human Bone Marrow-Derived Mesenchymal Stromal Cells." Cells Tissues Organs 201, no. 5 (2016): 354–65. http://dx.doi.org/10.1159/000444521.

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Tissue-engineered intervertebral discs (IVDs) utilizing decellularized extracellular matrix (ECM) could be an option for the reconstruction of impaired IVDs due to degeneration or injury. The objective of this study was to prepare a cell-free decellularized human IVD scaffold and to compare neotissue formation in response to recellularization with human IVD cells (hIVDCs) or human bone marrow-derived (hBM) mesenchymal stromal cells (MSCs). IVDs were decellularized via freeze-thaw cycles, detergents and trypsin. Histological staining was performed to monitor cell removal and glycosaminoglycan (GAG) removal. The decellularized IVD was preconditioned using bovine serum albumin and fetal bovine serum before its cytocompatibility for dynamically cultured hBM-MSCs (chondrogenically induced or not) and hIVDCs was compared after 14 days. In addition, DNA, total collagen and GAG contents were assessed. The decellularization protocol achieved maximal cell removal, with only few remaining cell nuclei compared with native tissue, and low toxicity. The DNA content was significantly higher in scaffolds seeded with hIVDCs compared with native IVDs, cell-free and hBM-MSC-seeded scaffolds (p < 0.01). The GAG content in the native tissue was significantly higher compared to the others groups except for the scaffolds reseeded with chondrogenically induced hBM-MSCs (p < 0.05). In addition, there was a significantly increased total collagen content in the chondrogenically induced hBM-MSCs group (p < 0.01) compared with the native IVDs, cell-free and hIVDC-seeded scaffolds (p < 0.01); both recolonizing cell types were more evenly distributed on the scaffold surface, but only few cells penetrated the scaffold. The resulting decellularized ECM was cytocompatible and allowed hBM-MSCs/hIVDCs survival and ECM production.

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Rakan, B., N. AlGarni, O. Salem, L. Epure, AA Habis, J. Antoniou, F. Mwale, and M. Grant. "Free calcium induces degenerative changes in the intervertebral disc through the calcium sensing receptor." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 42, S1 (May 2015): S50. http://dx.doi.org/10.1017/cjn.2015.226.

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Introduction: Degenerative disc disease (DDD) is a common cause of lower back pain. Calcification of the intervertebral disc (IVD) has been correlated with DDD. The role of IVD calcification in the development DDD is unknown. We noticed an increase in ionic calcium content and expression of the extracellular calcium-sensing receptor (CaSR) in the degenerate discs, however, its role in DDD remains unclear. Material and Methods: IVD Cells: Bovine and human NP and AF cells were incubated in culture media supplemented with various concentrations of calcium, and a CaSR agonist IVD Cultures: IVDs from bovine tails were isolated and the vertebral bone was removed. IVDs were cultured for 6 weeks in culture medium supplemented with calcium (1.0, 2.5, or 5.0 mM), or a CaSR agonist. Western blotting was performed on extracts to assess for aggrecan and Col II. Results: The expression of aggrecan and Col II decreased dose-dependently in both NP and AF cells, as well as in the organ culture model following supplementation with calcium or the CaSR agonist. Conclusion: Our results suggest that changes in the local concentrations of calcium are not benign, and that activation of the CaSR may be a contributing factor in IVD degeneration.

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Russo, Fabrizio, Luca Ambrosio, Marianna Peroglio, Wei Guo, Sebastian Wangler, Jan Gewiess, Sibylle Grad, et al. "A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study." International Journal of Molecular Sciences 22, no. 6 (March 15, 2021): 2963. http://dx.doi.org/10.3390/ijms22062963.

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The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 μL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

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Romaniyanto, Romaniyanto, Cita Rosita Sigit Prakoeswa, Damayanti Tinduh, Hari Basuki Notobroto, Fedik Abdul Rantam, Dwikora Novembri Utomo, Heri Suroto, and Ferdiansyah Ferdiansyah. "The potential of mesenchymal stem‐cell secretome for regeneration of intervertebral disc: A review article." Indonesian Journal of Biotechnology 26, no. 2 (June 28, 2021): 61. http://dx.doi.org/10.22146/ijbiotech.63318.

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Low back pain is a crucial public health problem that is commonly associated with intervertebral disc de‐ generation and has vast socio‐economic impact worldwide. Current treatments for disc degeneration are conservative, non‐surgical, or surgical interventions, and there is no current clinical therapy aimed at directly reversing the degeneration. Given the limited capacity of intervertebral disc (IVD) cells to self‐repair, treatment aiming to regenerate IVDs is a topic of interest and mesenchymal stem cells (MSCs) have been identified as having potential in this regeneration. Recent studies have revealed that the benefits of MSC therapy could result from the molecules the cells secrete and that play principal roles in regulating essential biologic processes, rather than from the implanted cells themselves. Therefore, the objective of this study is to review the potential use of the MSC secretome to regenerate IVDs. Current evidence shows that the secretome may regenerate IVDs by modulating the gene expressions of nucleus pulposus cells (upregulation of keratin 19 and downregulation of matrix metalloproteinase 12 and matrix Gla protein) and stimulating IVD progenitor cells to repair the degenerated disc.

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Roh, Eun, Anjani Darai, Jae Kyung, Hyemin Choi, Su Kwon, Basanta Bhujel, Kyoung Kim, and Inbo Han. "Genetic Therapy for Intervertebral Disc Degeneration." International Journal of Molecular Sciences 22, no. 4 (February 4, 2021): 1579. http://dx.doi.org/10.3390/ijms22041579.

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Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.

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Tang, Guoqing, Xiaoguang Han, Zhijie Lin, Hongbin Qian, Bing Chen, Chengliang Zhou, Yong Chen, and Weimin Jiang. "Propionibacterium acnes Accelerates Intervertebral Disc Degeneration by Inducing Pyroptosis of Nucleus Pulposus Cells via the ROS-NLRP3 Pathway." Oxidative Medicine and Cellular Longevity 2021 (February 1, 2021): 1–12. http://dx.doi.org/10.1155/2021/4657014.

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Our previous study verified the occurrence of Propionibacterium acnes (P. acnes), a low-virulence anaerobic bacterium, latently residing in degenerated intervertebral discs (IVDs), and the infection had a strong association with IVD degeneration. We explored whether P. acnes induces nucleus pulposus cell (NPC) pyroptosis, a more dangerous cell death process than apoptosis, and accelerates IVD degeneration via the pyroptotic products interleukin- (IL-) 1β and IL-18. After coculturing with P. acnes, human NPCs showed significant upregulation of NOD-like receptor 3 (NLRP3), cleaved IL-1β, cleaved caspase-1, and cleaved gasdermin D in response to the overexpression of IL-1β and IL-18 in a time- and dose-dependent manner. In addition, the gene expression of inflammatory factors and catabolic enzymes significantly increased in normal NPCs when cocultured with pyroptotic NPCs in a transwell system, and the adverse effects were inhibited when NPC pyroptosis was suppressed. Furthermore, inoculation of P. acnes into the IVDs of rats caused significant pyroptosis of NPCs and remarkable IVD degeneration. Finally, coculture of NPCs with P. acnes induced the overexpression of reactive oxygen species (ROS) and NLRP3, while inhibition of both factors reduced NPC pyroptosis. Therefore, P. acnes induces NPC pyroptosis via the ROS-NLRP3 signaling pathway, and the pyroptotic NPCs cause an IVD degeneration cascade. Targeting the P. acnes-induced pyroptosis of NPCs may become an alternative treatment strategy for IVD degeneration in the future.

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Ferreira, JR, GQ Teixeira, e. Neto, c. Ribeiro-Machado, AM Silva, J. Caldeira, C. Leite Pereira, et al. "IL-1β-pre-conditioned mesenchymal stem/stromal cells’ secretome modulates the inflammatory response and aggrecan deposition in intervertebral disc." European Cells and Materials 41 (April 20, 2021): 431–543. http://dx.doi.org/10.22203/ecm.v041a28.

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Mesenchymal stem/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1β (10 ng/mL) and low oxygen (6 % O2), mimicking the degenerative IVD. IL-1β-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3α, IL-6, IL-8 and GRO α/β/γ (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-γ, IL-10, IL-4, IL-5 and TNF-α (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based/ cell-free therapeutic approach to LBP.

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Yokozeki, Yuji, Ayumu Kawakubo, Masayuki Miyagi, Akiyoshi Kuroda, Hiroyuki Sekiguchi, Gen Inoue, Masashi Takaso, and Kentaro Uchida. "Reduced TGF-β Expression and CD206-Positive Resident Macrophages in the Intervertebral Discs of Aged Mice." BioMed Research International 2021 (July 12, 2021): 1–7. http://dx.doi.org/10.1155/2021/7988320.

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Age is a key factor in intervertebral disc (IVD) degeneration; however, the changes that occur in IVDs with age are not fully understood. Tissue-resident macrophages are critical for tissue homeostasis and are regulated by transforming growth factor- (TGF-) β. We examined changes in the proportion of resident macrophages in young versus aged mice and the role of TGF-β in regulating resident macrophages in IVDs. IVDs were harvested from 4-month (young) and 18-month-old (aged) C57BL/6J mice. The proportion of macrophages in IVDs was determined using flow cytometry ( n = 5 for each time point) and the expression of Cd11b, Cd206, and Tgfb genes, which encode CD11b, CD206, and TGF-β protein, respectively, using real-time PCR. To study the role of TGF-β in the polarization of resident macrophages, resident macrophages isolated from IVDs from young and aged mice were treated with recombinant TGF-β with and without a TGF-β inhibitor (SB431542). Additionally, SB431542 was intraperitoneally injected into young and aged mice, and Cd206 expression was examined using real-time PCR ( n = 10 for each time point). The proportion of CD11b+ and CD11b+ CD206+ cells was significantly reduced in aged versus young mice, as was Cd11b, Cd206, and Tgfb expression. TGF-β/IL10 stimulation significantly increased the expression of Cd206, an M2 macrophage marker, in disc macrophages from both young and aged mice. Meanwhile, administration of a TGF-β inhibitor significantly reduced Cd206 expression compared to vehicle control in both groups. Conclusion. Resident macrophages decrease with age in IVDs, which may be associated with the concomitant decrease in TGF-β. Our findings provide new insight into the mechanisms of age-related IVD pathology.

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Treffel, Loïc, Nastassia Navasiolava, Karen Mkhitaryan, Emmanuelle Jouan, Kathryn Zuj, Guillemette Gauquelin-Koch, Marc-Antoine Custaud, and Claude Gharib. "DI-5-Cuffs: Lumbar Intervertebral Disc Proteoglycan and Water Content Changes in Humans after Five Days of Dry Immersion to Simulate Microgravity." International Journal of Molecular Sciences 21, no. 11 (May 26, 2020): 3748. http://dx.doi.org/10.3390/ijms21113748.

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Most astronauts experience back pain after spaceflight, primarily located in the lumbar region. Intervertebral disc herniations have been observed after real and simulated microgravity. Spinal deconditioning after exposure to microgravity has been described, but the underlying mechanisms are not well understood. The dry immersion (DI) model of microgravity was used with eighteen male volunteers. Half of the participants wore thigh cuffs as a potential countermeasure. The spinal changes and intervertebral disc (IVD) content changes were investigated using magnetic resonance imaging (MRI) analyses with T1-T2 mapping sequences. IVD water content was estimated by the apparent diffusion coefficient (ADC), with proteoglycan content measured using MRI T1-mapping sequences centered in the nucleus pulposus. The use of thigh cuffs had no effect on any of the spinal variables measured. There was significant spinal lengthening for all of the subjects. The ADC and IVD proteoglycan content both increased significantly with DI (7.34 ± 2.23% and 10.09 ± 1.39%, respectively; mean ± standard deviation), p < 0.05). The ADC changes suggest dynamic and rapid water diffusion inside IVDs, linked to gravitational unloading. Further investigation is needed to determine whether similar changes occur in the cervical IVDs. A better understanding of the mechanisms involved in spinal deconditioning with spaceflight would assist in the development of alternative countermeasures to prevent IVD herniation.

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Hansen, Tove, Lucas A. Smolders, Marianna A. Tryfonidou, Björn P. Meij, Johannes C. M. Vernooij, Niklas Bergknut, and Guy C. M. Grinwis. "The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs." Veterinary Pathology 54, no. 6 (August 29, 2017): 945–52. http://dx.doi.org/10.1177/0300985817726834.

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Since the seminal work by Hans-Jörgen Hansen in 1952, it has been assumed that intervertebral disc (IVD) degeneration in chondrodystrophic (CD) dogs involves chondroid metaplasia of the nucleus pulposus, whereas in nonchondrodystrophic (NCD) dogs, fibrous metaplasia occurs. However, more recent studies suggest that IVD degeneration in NCD and CD dogs is more similar than originally thought. Therefore, the aim of this study was to compare the histopathology of IVD degeneration in CD and NCD dogs. IVDs with various grades of degeneration (Thompson grade I–III, n = 7 per grade) from both CD and NCD dogs were used (14 CD and 18 NCD dogs, 42 IVDs in total). Sections were scored according to a histological scoring scheme for canine IVD degeneration, including evaluation of the presence of fibrocyte-like cells in the nucleus pulposus. In CD dogs, the macroscopically non-degenerated nucleus pulposus contained mainly chondrocyte-like cells, whereas the non-degenerated nucleus pulposus of NCD dogs mainly contained notochordal cells. The histopathological changes in degenerated discs were similar in CD and NCD dogs and resembled chondroid metaplasia. Fibrocytes were not seen in the nucleus pulposus, indicating that fibrous degeneration of the IVD was not present in any of the evaluated grades of degeneration. In conclusion, intervertebral disc degeneration was characterized by chondroid metaplasia of the nucleus pulposus in both NCD and CD dogs. These results revoke the generally accepted concept that NCD and CD dogs suffer from a different type of IVD degeneration, in veterinary literature often referred to as chondroid or fibroid degeneration, and we suggest that chondroid metaplasia should be used to describe the tissue changes in the IVD in both breed types.

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Melvin, Tom, and Marina Torre. "New medical device regulations: the regulator’s view." EFORT Open Reviews 4, no. 6 (June 2019): 351–56. http://dx.doi.org/10.1302/2058-5241.4.180061.

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Advances in medical device technology have been dramatic in recent years resulting in both an increased number of medical devices and an increase in the invasiveness and critical function which devices perform. Two new regulations entered into force in Europe in May 2017, the Medical Device Regulation (MDR) and the In Vitro Diagnostic Device Regulation (IVDR). These regulations will replace the current directives over the coming years. These regulations, for the first time introduce requirements relating to registries. Medical device manufacturers are required to have systematic methods for examining their devices once available on the market, by systematically gathering, recording and analysing data on safety and performance. Registries can assist public health protection in very practical ways, for example, to help urgently identify patients or devices. Registries can also be powerful tools for collecting and appraising real-world clinical evidence concerning medical devices. Clinical investigations are limited in terms of the sample size and the duration of follow-up which can reasonably be expected. Registries may also be the only available tool to examine rare adverse effects, sub-populations or for time durations which it is not possible or feasible to study in a clinical investigation. By ensuring that a core dataset is collected which can be compared to other registries or trial data, it is possible to pool data to better examine outcomes. There are a range of excellent initiatives which have aimed at ensuring the appropriate regulatory application of registry data. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180061

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Joshi, Abhijeet, Samir Mehta, Edward Vresilovic, Andrew Karduna, and Michele Marcolongo. "Nucleus Implant Parameters Significantly Change the Compressive Stiffness of the Human Lumbar Intervertebral Disc." Journal of Biomechanical Engineering 127, no. 3 (January 31, 2005): 536–40. http://dx.doi.org/10.1115/1.1894369.

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Nucleus replacement by a synthetic material is a recent trend for treatment of lower back pain. Hydrogel nucleus implants were prepared with variations in implant modulus, height, and diameter. Human lumbar intervertebral discs (IVDs) were tested in compression for intact, denucleated, and implanted condition. Implantation of nucleus implants with different material and geometric parameters into a denucleated IVD significantly altered the IVD compressive stiffness. Variations in the nucleus implant parameters significantly change the compressive stiffness of the human lumbar IVD. Implant geometrical variations were more effective than those of implant modulus variations in the range examined.

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Vasilikos, Ioannis, Graciosa Q. Teixeira, Andreas Seitz, Julia Nothelfer, Julian Haas, Hans-Joachim Wilke, Boris Mizaikoff, Jürgen Beck, Ulrich Hubbe, and Cornelia Neidlinger-Wilke. "Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc." PLOS ONE 16, no. 6 (June 3, 2021): e0252672. http://dx.doi.org/10.1371/journal.pone.0252672.

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Background Collagen cross-links contribute to the mechanical resilience of the intervertebral disc (IVD). UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) is a well-established and effective ophthalmological intervention that increases the mechanical rigidity of the collagen-rich corneal matrix in Keratoconus. This study explores the feasibility, safety and efficacy of translating this intervention in reinforcing the IVD. Methods Annulus fibrosus (AF) cells were isolated from bovine IVDs and treated with different combinations of riboflavin (RF) concentrations (0.05–8 mM) and UVA light intensities (0.3–4 mW/cm2). Metabolic activity (resazurin assay), cell viability (TUNEL assay), and gene expression of apoptosis regulators C-FOS and PT5 were assessed immediately and 24 hours after treatment. Biomechanical effects of UVA-CXL on IVDs were measured by indentation analysis of changes in the instantaneous modulus and by peel-force delamination strength analysis of the AF prior and after treatment. Results Different intensities of UVA did not impair the metabolic activity of AF cells. However, RF affected metabolic activity (p < 0.001). PT53 expression was similar in all RF conditions tested while C-FOS expression decreased 24 hours after treatment. Twenty-four hours after treatment, no apoptotic cells were observed in any condition tested. Biomechanical characterizations showed a significant increase in the annular peel strength of the UVA-CXL group, when compared to controls of UVA and RF alone (p < 0.05). UVA-CXL treated IVDs showed up to 152% higher (p < 0.001) instantaneous modulus values compared to the untreated control. Conclusion This is the first study on UVA-CXL treatment of IVD. It induced significantly increased delamination strength and instantaneous modulus indentation values in intact IVD samples in a structure–function relationship. RF concentrations and UVA intensities utilized in ophthalmological clinical protocols were well tolerated by the AF cells. Our findings suggest that UVA-CXL may be a promising tool to reinforce the IVD matrix.

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Feng, Chencheng, Minghui Yang, Minghong Lan, Chang Liu, Yang Zhang, Bo Huang, Huan Liu, and Yue Zhou. "ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/5601593.

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Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD.

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Wollschläger, Lena M., Sven Nebelung, Christoph Schleich, Anja Müller-Lutz, Karl L. Radke, Miriam Frenken, Matthias Boschheidgen, et al. "Evaluating Lumbar Intervertebral Disc Degeneration on a Compositional Level Using Chemical Exchange Saturation Transfer: Preliminary Results in Patients with Adolescent Idiopathic Scoliosis." Diagnostics 11, no. 6 (May 22, 2021): 934. http://dx.doi.org/10.3390/diagnostics11060934.

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Lumbar intervertebral disc (IVD) degeneration is characterized by structural and compositional changes. This study aimed to assess the glycosaminoglycan (GAG) content of IVDs of patients with adolescent idiopathic scoliosis (AIS) and healthy controls using GAG chemical exchange saturation transfer (gagCEST) imaging. Ten AIS patients (mean age 18.3 ± 8.2 years) and 16 healthy controls (mean age 25.5 ± 1.7 years) were included. Clinical standard morphologic MR images (T1w-, T2w-, and STIR-sequences), to rule out further spinal disorders and assess IVD degeneration using the Pfirrmann score, and compositional gagCEST sequences were acquired on a 3T MRI. In AIS patients, the most distal scoliotic curve was determined on whole-spine conventional radiographs and morphological MRI and IVDs were divided as to whether they were affected by scoliotic deformity, i.e., proximal (affected, aIVDs) or distal (unaffected, uaIVDs) to the stable vertebra of the most distal scoliotic curve. Linear mixed models were used to compare mean gagCEST-values. Over all segments, AIS-patients’ IVDs exhibited significantly lower gagCEST-values than the controls: 2.76 [2.32, 3.20]% (AIS), 3.51 [3.16, 3.86]% (Control); p = 0.005. Meanwhile, no significant differences were found for gagCEST values comparing aIVDs with uaIVDs. In conclusion, as a powerful diagnostic adjunct, gagCEST imaging may be prospectively applied to detect early compositional degenerative changes in patients suffering from AIS.

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Bisson, DG, M. Mannarino, R. Racine, and L. Haglund. "For whom the disc tolls: intervertebral disc degeneration, back pain and toll-like receptors." European Cells and Materials 41 (March 19, 2021): 355–69. http://dx.doi.org/10.22203/ecm.v041a23.

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Intervertebral disc (IVD) degeneration is characterised by catabolic and inflammatory processes that contribute largely to tissue degradation and chronic back pain. The disc cells are responsible for the pathological production of pro-inflammatory cytokines and catabolic enzymes leading to degeneration. However, this phenotypical change is poorly understood. Growing evidence in animal and human studies implicates Toll-like receptors (TLR) and their activation through danger-associated alarmins, found increasingly in degenerating IVDs. TLR signalling results in the release of pro-inflammatory cytokines and proteolytic enzymes that can directly cause IVD degeneration and back pain. This review aims to summarise the current literature on TLR activation in IVD degeneration and discuss potential treatment modalities to alleviate the inflammatory phenotype of disc cells in order to arrest IVD degeneration and back pain.

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Hu, Binwu, Ruijun He, Kaige Ma, Zhe Wang, Min Cui, Hongzhi Hu, Saroj Rai, Baichuan Wang, and Zengwu Shao. "Intervertebral Disc-Derived Stem/Progenitor Cells as a Promising Cell Source for Intervertebral Disc Regeneration." Stem Cells International 2018 (December 18, 2018): 1–11. http://dx.doi.org/10.1155/2018/7412304.

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Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain. Despite remarkable improvements in both pharmacological and surgical management of IVD degeneration (IVDD), therapeutic effects are still unsatisfactory. It is because of the fact that these therapies are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD. Accumulating evidence has revealed that the endogenous stem/progenitor cells exist in the IVD, and these cells might be a promising cell source in the regeneration of degenerated IVD. However, the biological characteristics and potential application of IVD-derived stem/progenitor cells (IVDSCs) have yet to be investigated in detail. In this review, the authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVD. The authors believe that this review exclusively address the current understanding of IVDSCs and provide a novel approach for the IVD regeneration.

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Bischof, Muriel C., Sonja Häckel, Andrea Oberli, Andreas S. Croft, Katharina A. C. Oswald, Christoph E. Albers, Benjamin Gantenbein, and Julien Guerrero. "Influence of Angiopoietin Treatment with Hypoxia and Normoxia on Human Intervertebral Disc Progenitor Cell’s Proliferation, Metabolic Activity, and Phenotype." Applied Sciences 11, no. 15 (August 2, 2021): 7144. http://dx.doi.org/10.3390/app11157144.

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Increasing evidence implicates intervertebral disc (IVD) degeneration as a major contributor to low back pain. In addition to a series of pathogenic processes, degenerated IVDs become vascularized in contrast to healthy IVDs. In this context, angiopoietin (Ang) plays a crucial role and is involved in cytokine recruitment, and anabolic and catabolic reactions within the extracellular matrix (ECM). Over the last decade, a progenitor cell population has been described in the nucleus pulposus (NP) of the IVD to be positive for the Tie2 marker (also known as Ang-1 receptor). In this study, we investigated the influence of Ang-1 and Ang-2 on human NP cell (Tie2+, Tie2− or mixed) populations isolated from trauma patients during 7 days in normoxia (21% O2) or hypoxia (≤5% O2). At the end of the process, the proliferation and metabolic activity of the NP cells were analyzed. Additionally, the relative gene expression of NP-related markers was evaluated. NP cells showed a higher proliferation depending on the Ang treatment. Moreover, the study revealed higher NP cell metabolism when cultured in hypoxia. Additionally, the relative gene expression followed, with an increase linked to the oxygen level and Ang concentration. Our study comparing different NP cell populations may be the start of new approaches for the treatment of IVD degeneration.

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Ying, Jinwei, Zhihua Han, Shishen Pei, Linghao Su, and Dike Ruan. "Effects of Stromal Cell-Derived Factor-1α Secreted in Degenerative Intervertebral Disc on Activation and Recruitment of Nucleus Pulposus-Derived Stem Cells." Stem Cells International 2019 (November 19, 2019): 1–14. http://dx.doi.org/10.1155/2019/9147835.

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Stromal cell-derived factor-1α (SDF-1α) plays a significant role in mobilizing and recruiting mesenchymal stem cells (MSCs) to the sites of injury. This study investigated the potential of SDF-1α released in the degenerative intervertebral disc (IVD) to activate and recruit endogenous nucleus pulposus-derived stem cells (NPSCs) for regeneration in situ. We found SDF-1α was highly expressed and secreted by the native disc cells when cultured in the proinflammatory mediators in vitro mimicking the degenerative settings. Immunohistochemical staining also showed that the expression level of SDF-1α was significantly higher in the degenerative group compared to that in the normal group. In addition to enhancement of viability, SDF-1α significantly increased the number of NPSCs migrating into the center of the nucleotomized bovine IVD ex vivo. After the systemic delivery of exogenous PKH26-labelled NPSCs into the rats in vivo, there was a significant difference in the distribution of the migrated cells between the normal and the degenerative IVDs, which might be caused by the different expression levels of SDF-1α. However, blocking CXC chemokine receptor 4 (CXCR4) with AMD3100 effectively abrogated SDF-1α-stimulated proliferation and migration. Taken together, SDF-1α may be a key chemoattractant that is highly produced in response to the degenerative changes, which can be used to enhance the proliferation and recruitment of endogenous stem cells into the IVDs. These findings may be of importance for understanding IVD regenerative mechanisms and development of regenerative strategies in situ for IVD degeneration.

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Hoffman, Haydn, Aaron W. Choi, Victor Chang, Jon Kimball, Alan S. Verkman, Rubeen Virani, Brian Kim, Tianyi Niu, and Daniel C. Lu. "Aquaporin-1 Expression in Herniated Human Lumbar Intervertebral Discs." Global Spine Journal 7, no. 2 (April 2017): 133–40. http://dx.doi.org/10.1177/2192568217694007.

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Study Design: Case series. Objective: Intervertebral disc (IVD) degeneration is the cause of spondylosis. The pathogenesis is poorly understood, but disc dehydration often plays a role. In this study, we aim to identify and quantify aquaporin-1 (AQP1) in ex vivo human degenerated IVDs obtained intraoperatively and to investigate the relationship between AQP1 levels and magnetic resonance imaging (MRI) T2 intensity of the disc. Methods: Ex vivo samples of nucleus pulposus (NP) tissue from lumbar IVDs were obtained from 18 consecutive patients who underwent surgery for disc herniation at L4/5 and L5/S1 level. Immunohistochemistry was performed to determine the presence of AQP1 expression, and this was quantified by Western blot analysis. AQP1 expression was compared to preoperative IVD signal intensity on T2-weighted MRI. Results: NP tissue was obtained from 18 patients (9 for L4/5 level and 9 for L5/S1 level). AQP1 expression was detected in all samples by Western blot and immunohistochemistry. AQP1 expression had a linear correlation with the preoperative IVD signal intensity on T2-weighted MRI at L4/5 level ( R2 = 0.90) and at L5/S1 level ( R2 = 0.92). AQP1 expression was 52.2 ± 59.0 at L5/S1 level and 15.9 ± 20.6 at L4/5 ( P = .10). Conclusions: Our results show that AQP1 can be detected in IVD obtained from live human subjects. Increased AQP1 expression is associated with greater disc hydration as measured by signal intensity on T2-weighted MRI. AQP1 may have a role in the dehydration associated with disc degeneration.

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Freling, Gabriel Fernando, Bernardo Garziera Gasperin, Rogério Ferreira, Matheus Pedroti Cesaro, João Francisco Oliveira, Vilceu Bordignon, and Paulo Bayard Dias Gonçalves. "Delaying farrowing using intravaginal devices impregnated with progestagen does not affect the proportion of piglets born alive." Ciência Rural 43, no. 7 (June 11, 2013): 1258–64. http://dx.doi.org/10.1590/s0103-84782013005000077.

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The objective of this study was to evaluate the efficiency of progestagen intravaginal devices (IVDs) in preventing parturition in sows by determining the effect of delaying parturition on the alive/total born piglets ratio. Evaluations of IVDs containing 0.5, 1.0 or 1.5g progesterone (P4) showed they were not effective in delaying parturition at any dosage tested. In a second experiment, seventy-five sows at day 112 of pregnancy were equally distributed (n=15 per group) in the following treatments: prostaglandin (PGF2α; 250µg sodium cloprostenol; control group) or PGF2α and simultaneous insertion of an IVD containing medroxyprogesterone acetate (MPA) for 48h. Control sows initiated labor 27.7±1.6h after PGF2α injection. The mean time (±SEM) between PGF2α administration and parturition was 72.1±8.8h, 72.7±3.8h, 82.7±7.1h and 81.8±3.5h for MPA 100, 200, 400 and 800mg, respectively, differing from control group (P<0.05). To evaluate the effect of delaying parturition on the alive/total born piglets ratio at birth, sows between days 109 and 112 of gestation received IVDs containing 800mg MPA (on Thursdays) for 72h to prevent parturition in weekends and then were treated with PGF2α at the time of device withdrawal (on Sundays). The alive/total born piglets ratio was 89.0±1.6, 90.1±1.2 and 89.0±1.5% for control (Normal group; n=57 sows), PGF2α-induced (Induced group; n=57 sows), and IVD+PGF2α-induced (MPA800 group, n=56 sows) groups, respectively (P>0.05). These findings confirm that IVDs impregnated with MPA can effectively prevent parturition in sows without affecting the alive/total born piglets ratio and therefore represent an alternative to avoid weekend farrowing in swine herds.

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Kameda, Takuya, Joel Zvick, Miriam Vuk, Aleksandra Sadowska, Wai Kit Tam, Victor Y. Leung, Kata Bölcskei, et al. "Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling." International Journal of Molecular Sciences 20, no. 7 (April 10, 2019): 1767. http://dx.doi.org/10.3390/ijms20071767.

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Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 µM), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 µM AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.

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Journal articles on the topic 'IVDR'

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