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1

Nokhbehsaim, Marjan, Anna Damanaki, Andressa Vilas Boas Nogueira, Sigrun Eick, Svenja Memmert, Xiaoyan Zhou, Shanika Nanayakkara, et al. "Regulation of Ghrelin Receptor by Periodontal Bacteria In Vitro and In Vivo." Mediators of Inflammation 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/4916971.

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Ghrelin plays a major role in obesity-related diseases which have been shown to be associated with periodontitis. This study sought to analyze the expression of the functional receptor for ghrelin (GHS-R1a) in periodontal cells and tissues under microbial conditions in vitro and in vivo. The GHS-R1a expression in human periodontal cells challenged with the periodontopathogen Fusobacterium nucleatum, in gingival biopsies from periodontally healthy and diseased individuals, and from rats with and without ligature-induced periodontitis was analyzed by real-time PCR, immunocytochemistry, and immunofluorescence. F. nucleatum induced an initial upregulation and subsequent downregulation of GHS-R1a in periodontal cells. In rat experimental periodontitis, the GHS-R1a expression at periodontitis sites was increased during the early stage of periodontitis, but significantly reduced afterwards, when compared with healthy sites. In human gingival biopsies, periodontally diseased sites showed a significantly lower GHS-R1a expression than the healthy sites. The expression of the functional ghrelin receptor in periodontal cells and tissues is modulated by periodontal bacteria. Due to the downregulation of the functional ghrelin receptor by long-term exposure to periodontal bacteria, the anti-inflammatory actions of ghrelin may be diminished in chronic periodontal infections, which could lead to an enhanced periodontal inflammation and tissue destruction.
2

Mancini, Leonardo, Adriano Fratini, and Enrico Marchetti. "Periodontal Regeneration." Encyclopedia 1, no. 1 (January 13, 2021): 87–98. http://dx.doi.org/10.3390/encyclopedia1010011.

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Periodontal regeneration is a technique that aims to regenerate the damaged tissue around periodontally compromised teeth. The regenerative process aims to use scaffolds, cells, and growth factors to enhance biological activity.
3

Nighojkar, Urvashi Rajeev, Dr Priya A. Lele, and Mudita Agrawal. "Scope of Stem Cells in Periodontal Regeneration." International Journal of Scientific Research 2, no. 5 (June 1, 2012): 428–31. http://dx.doi.org/10.15373/22778179/may2013/145.

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4

Karunanithi Arulvizhi M, Arunagiri. "Stem Cells in Periodontal Regenerations - A Review." International Journal of Science and Research (IJSR) 13, no. 2 (February 5, 2024): 589–94. http://dx.doi.org/10.21275/sr24206105401.

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5

Gonçalves, Gabriela Sumie Yaguinuma, Tayna Natsumi Takakura, Anderson Catelan, Rosalinda Tanuri Zaninotto Venturim, Carolina dos Santos Santinoni, and Christine Men Martins. "Tratar ou extrair? Tratamento de lesão endoperiodontal, um relato de caso clínico." ARCHIVES OF HEALTH INVESTIGATION 9, no. 6 (April 20, 2020): 535–40. http://dx.doi.org/10.21270/archi.v9i6.4814.

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Introdução: Lesões endoperiodontais são lesões originadas de produtos inflamatórios encontrados tanto em periodonto quanto em polpa. Tais lesões podem se originar devido a uma infecção pulpar ou periodontal. Visando o prognóstico favorável, é imprescindível o conhecimento da etiologia, realização do correto diagnóstico e elaboração do plano de tratamento que envolve o tratamento endodôntico precedido do tratamento periodontal. Objetivo: O propósito do presente trabalho foi de relatar um caso clínico de lesão endoperiodontal e o tratamento realizado. Relato de caso clínico: Paciente gênero feminino, 51 anos, compareceu à clínica com uma fístula na região do dente 46, procedeu-se com exame radiográfico, rastreamento de fístula, testes endodônticos e avaliação periodontal. Foi diagnosticada lesão endoperiodontal. Executou-se, então, o tratamento endodôntico em sessões múltiplas, utilizando hidróxido de cálcio como medicação intracanal e o tratamento periodontal concomitante; finalizou-se endodontia obturando-se os canais radiculares. Conclusão: Observou-se, no controle, que a associação de tratamentos foi eficaz e houve melhora significativa do quadro, constatando-se silêncio clínico e sucesso do tratamento. Realizar o tratamento conservador a despeito da exodontia foi a melhor escolha para a paciente. Descritores: Endodontia; Periodontia; Polpa Dentária; Periodonto. Referências Sunitha VR, Emmadi P, Namasivayam A, Thyegarajan R, Rajaraman V. The periodontal - endodontic continuum A review. J Conserv Dent. 2008;11(2):54-62. Betancourt P, Elgueta R, Fuentes R. Treatment of endo-periodontal lesion using leukocyte-platelet-rich fibrin - a case report. Colomb Med. 2017;48(4):204-7. Lopes HP, Siqueira JF. Endodontia: Biologia e Técnica. Rio de Janeiro: Medsi-Guanabara Koogan; 2015. Lindhe J, Karring T, Lang NP. Tratado de periodontia clínica e implantologia oral. Rio de Janeiro: Guanabara Koogan; 2010. Anand V, Govila V, Gulati M. Endo-perio lesion part II (the treatment) - a review. 2012;3(1):10-6. Rotstein I, Simon JH. Diagnosis, prognosis and decision-making in the treatment of combined periodontal-endodontic lesions. J Periodontol. 2004;34:165-203. Parolia A, Gait TC, Porto ICCM, Mala K. Endo-perio lesion: a dilemma from 19th until 21st century. J Interdisp Dent. 2013;3(1):2-11. Kim E, Song JS, Jung IY, Lee SJ, Kim S. Prospective clinical study evaluating endodontic microsurgery outcomes for cases with lesions of endodontic origin compared with cases with lesions of combined periodontal-endodontic origin. J Endod. 2008;34(5):546-51. Heasman PA. An endodontic conundrum: the association between pulpal infection and periodontal disease. Br Dent J. 2014;216(6):275-9. Schmidt JC, Walter C, Amato M, Weiger R. Treatment of periodontal-endodontic lesions--a systematic review. J Clin Periodontol. 2014; 41(8):779-90. Jivoinovici R, Suciu I, Dimitriu B, Perlea P, Bartok R, Malita M, Ionescu C. Endo-periodontal lesion--endodontic approach. J Med Life. 2014;7(4):542-44. Estrela C. Endodontia laboratorial e clínica, Série Abeno: Odontologia Essencial - Parte Clínica. São Paulo: Artes Médicas; 2013. Vera J, Siqueira JF Jr, Ricucci D, Loghin S, Fernández N, Flores B et al. One-versus two-visit endodontic treatment of teeth with apical periodontitis: a histobacteriologic study. J Endod. 2012;38(8):1040-52. Mohammadi Z, Dummer PMH. Properties and applications of calcium hydroxide in endodontics and dental traumatology. Inter Endod J. 2011;44(8):697-730. Batista VES, Olian DA, Mori GG. Diffusion of hydroxyl ions from calcium hydroxide and aloe vera pastes. Braz Dent J. 2014;25(3):212-16. Pereira TC, da Silva Munhoz Vasconcelos LR, Graeff MSZ, Ribeiro MCM, Duarte MAH, de Andrade FB. Intratubular decontamination ability and physicochemical properties of calcium hydroxidepastes. Clin Oral Investig. 2019;23(3):1253-62. Andolfatto C, da Silva GF, Cornélio AL, Guerreiro-Tanomaru JM, Tanomaru-Filho M, Faria G, Bonetti-Filho I, Cerri PS. Biocompatibility of intracanal medications based on calcium hydroxide. ISRN Dent. 2012;2012:904963. Duque TM, Prado M, Herrera DR, Gomes BPFA. Periodontal and endodontic infectious/inflammatory profile in primary periodontal lesions with secondary endodontic involvement after a calcium hydroxide-based intracanal medication. Clin Oral Investig. 2019;23(1):53-63. Kim D, Kim E. Antimicrobial effect of calcium hydroxide as an intracanal medicament in root canal treatment: a literature review - Part I. In vitro studies. Restor Dent Endod. 2014; 39(4):241-52. Adl A, Motamedifar M, Shams MS, Mirzaie A. Clinical investigation of the effect of calcium hydroxide intracanal dressing on bacterial lipopolysaccharide reduction from infected root canals. Aust Endod J. 2015;41(1):12-6. Hilton TJ, Ferracane JL, Mancl L; Northwest Practice-based Research Collaborative in Evidence-based Dentistry (NWP). Comparison of CaOH with MTA for direct pulp capping: a PBRN randomized clinical trial. J Dent Res. 2013;92(7 Suppl):16S-22S. Labban N, Yassen GH, Windsor LJ, Platt JA. The direct cytotoxic effects of medicaments used in endodontic regeneration on human dental pulp cells. Dent Traumatol. 2014;30(6):429-34. McIntyre PW, Wu JL, Kolte R, Zhang R, Gregory RL, Bruzzaniti A, Yassen GH. The antimicrobial properties, cytotoxicity, and differentiation potential of double antibiotic intracanal medicaments loaded into hydrogel system. Clin Oral Investig. 2019;23(3):1051-59. Bergenholtz, G., Hasselgren, G. Endodontics and periodontics. In: Lindhe, K., Karring, T., Lang, N. Clinical periodontology and implant dentistry. Copenhagen:Munksgaard; 2015. Harrington GW, Steiner DR, Ammons WF. The periodontal-endodontic controversy. Periodontol 2000. 2002;30:123-30. Fernandes LA, Martins TM, Almeida JM, Nagata MJ, Theodoro LH, Garcia VG, Bosco AF. Experimental periodontal disease treatment by subgingival irrigation with tetracycline hydrochloride in rats. J Appl Oral Sci. 2010;18(6):635-40. Storrer CM, Bordin GM, Pereira TT. How to diagnose and treat periodontal endodontic lesions? 2012;9(4):427-33. Verma PK, Srivastava R, Gupta KK, Srivastava A. Combined endodontic periodontal lesions: A clinical dilema. J Interdiscip Dent. 2011;1(2):119-24. Oh SL, Fouad AF, Park SH. Treatment strategy for guided tissue regeneration in combined endodontic-periodontal lesions: case report and review. J Endod. 2009;35(10):1331-36. Malli R, Lele P, Vishakha. Guided tissue regeneration in communicating periodontal and endodontic lesions - a hope for the hopeless. J Indian Soc Periodontol. 2011;15(4):410-13. Ghezzi C, Virzì M, Schupbach P, Broccaioli A, Simion M. Treatment of combined endodontic-periodontic lesions using guided tissue regeneration: clinical case and histology. Int J Periodontics Restorative Dent. 2012;32(4):433-9. Sun J, Liu Q. [Bio-Oss collagen bone grafting in the treatment of endodontic-periodontic lesion]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(9):1905-6. Sharma R, Hegde V, Siddharth M, Hegde R, Manchanda G, Agarwal P. Endodontic-periodontal microsurgery for combined endodontic-periodontal lesions: An overview. J Conserv Dent. 2014;17(6):510-16. Li Y, Wang X, Xu J, Zhou X, Xie K. [The clinical study on the use of diode laser irradiation in the treatment of periodontal-endodontic combined lesions]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2012;30(2):161-64, 168. Narang S, Narang A, Gupta R. A sequential approach in treatment of perio-endo lesion. J Indian Soc Periodontol. 2011;15(2):177-80. Pereira AL, Orzechowski PR, Filho SB, Cortelli JR. Subepithelial connective tissue graft: an alternative application for treating endoperiodontal lesions. Gen Dent. 2013;61(2):50-3. Yoneda M, Motooka N, Naito T, Maeda K, Hirofuji T. Resolution of furcation bone loss after non-surgical root canal treatment: application of a peptidase-detection kit for treatment of type I endoperiodontal lesion. J Oral Sci. 2005; 47(3):143-47. Shenoy N, Shenoy A. Endo-perio lesions: diagnosis and clinical considerations. Indian J Dent Res. 2010;21(4):579-85. Gerritsen AE, Allen PF, Witter DJ, Bronkhorst EM, Creugers NH. Tooth loss and oral health-related quality of life: a systematic review and meta-analysis. Health Qual Life Outcomes. 2010;8:126.
6

Fabila-Plata, Miriam Susana, and Rosa Diana Hernández Palacios. "Tratamiento de la enfermedad periodontal con células troncales de origen pulpar, en un adulto mayor. Caso clínico." Casos y Revisiones de Salud 3, no. 1 (July 1, 2021): 32–39. http://dx.doi.org/10.22201/fesz.26831422e.2021.3.1.4.

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Introducción. La enfermedad periodontal (EP) es un padecimiento de tipo inflamatorio crónico y con frecuencia causa pérdida dental en los adultos mayores. Su tratamiento se orienta a la regeneración de los tejidos periodontales a través de la eliminación de los agentes infecciosos presentes en el periodonto y en la sustitución del hueso alveolar perdido. Caso clínico. Paciente femenina de 61 años de edad que acudió a consulta estomatológica por presentar movilidad dental. En la valoración bucal se observó enfermedad periodontal. Se realizaron las tres fases de la terapia periodontal con aplicación de células troncales mesenquimales (Mesenchymal Stem Cells, MSC) de origen pulpar, mostrando disminución de la profundidad al sondaje y aumento en el nivel de inserción clínica. Conclusiones. Los hallazgos sugieren que la terapia periodontal regenerativa con MSC de origen pulpar representan una opción para el tratamiento de los defectos óseos ocasionados por la EP en los adultos mayores; sin embargo, es necesario llevar a cabo ensayos clínicos controlados y aumentar el tamaño de la muestra para recomendar su aplicación en la práctica clínica.
7

Song, In Seok, Yoon Sic Han, Joo-Hee Lee, Soyoun Um, Hui Young Kim, and Byoung Moo Seo. "Periodontal Ligament Stem Cells for Periodontal Regeneration." Current Oral Health Reports 2, no. 4 (August 27, 2015): 236–44. http://dx.doi.org/10.1007/s40496-015-0060-0.

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8

Aditya, Vangara, and Kharidhi Laxman Vandana. "Management of endo-perio lesion with autologous stem cell therapy." Saudi Journal of Oral Sciences 11, no. 1 (January 2024): 54–59. http://dx.doi.org/10.4103/sjoralsci.sjoralsci_79_23.

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The objective of periodontal therapy is the regeneration of tooth-supporting tissues. Various treatment modalities, such as the use of bone grafting materials, guided tissue regeneration, and delivery of enamel matrix derivatives or growth factors, are applied with large variability in regenerative outcomes. However, a case report was done by utilization of autologous dental pulp stem cells and periodontal ligament stem cell niches in the treatment of bone loss associated with endodontically and periodontally involved teeth. An autologous periodontal ligament stem cells niche adherent to the root and dental pulpal stem cells from dental pulp directly into the selected osseous defect following extraction of the impacted tooth in the same patient. The results of this case reported that the dental pulpal stem cells and periodontal ligament stem cells niche with gelatin sponge resulted in a significant amount of bone fill and reduction in probing pocket depth.
9

Hosokawa, Yoshitaka, Ikuko Hosokawa, Satoru Shindo, Kazumi Ozaki та Takashi Matsuo. "IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells". Cellular Physiology and Biochemistry 38, № 1 (2016): 153–59. http://dx.doi.org/10.1159/000438617.

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Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs). Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions.
10

Kramer, P. R., S. Nares, S. F. Kramer, D. Grogan, and M. Kaiser. "Mesenchymal Stem Cells Acquire Characteristics of Cells in the Periodontal Ligament in vitro." Journal of Dental Research 83, no. 1 (January 2004): 27–34. http://dx.doi.org/10.1177/154405910408300106.

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Mesenchymal stem cells differentiate into multiple types of cells derived from mesenchyme. Periodontal ligament cells are primarily derived from mesenchyme; thus, we expected mesenchymal stem cells to differentiate into periodontal ligament. Using a combination of immunohistochemistry and in situ hybridization on co-cultures of mesenchymal stem cells and periodontal ligament, we observed a significant increase in mesenchymal stem cells’ expression of osteocalcin and osteopontin and a significant decrease in expression of bone sialoprotein, characteristics of periodontal ligament in vivo. Increased osteopontin and osteocalcin and decreased bone sialoprotein expression was detected within 7 days and maintained through 21 days of co-culture. We conclude that contact or factors from periodontal ligament induced mesenchymal stem cells to obtain periodontal-ligament-like characteristics. Importantly, analysis of the data suggests the feasibility of utilizing mesenchymal stem cells in clinical applications for repairing and/or regenerating periodontal tissue.
11

Saito, A., E. Saito, M. Kawanami, and A. Shimada. "Healing in Transplanted Teeth with Periodontal Ligament Cultured In Vitro." Cell Transplantation 12, no. 5 (July 2003): 519–25. http://dx.doi.org/10.3727/000000003108747082.

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Regeneration of connective tissue attachment is the ultimate goal of periodontal therapy. It has been suggested that periodontal ligament cells possess the potential to create new connective tissue attachment. However, as cells from gingiva and alveolar bone occupy the root surface during initial wound healing, population by periodontal ligament cells is limited in vivo. We have been developing a new periodontal regeneration technique using in vitro tissue culture of periodontal ligament remaining on a periodontally involved root. The purpose of this study was to examine the periodontal healing after transplantation of teeth with reduced periodontal ligament that had been cultured in vitro. Twenty-five incisors from four beagles were used. After the teeth were extracted, the periodontal ligament and cementum were removed from coronal part of the roots and the roots were planed. The periodontal ligament of the apical part was retained. Fourteen teeth of the experimental group were transplanted following culture for 6 weeks. Eleven teeth of the control group were similarly prepared and immediately transplanted without tissue culture. Four weeks after transplantation, the specimens were prepared for histological analysis. Downgrowth of junctional epithelium on the root of experimental group was significantly less than control. Most of the root planed surfaces of experimental group were covered with periodontal ligament fibers oriented parallel or inclined to the root surfaces and limited new cementum formation was observed near the apical end of the planed root. There was no significant difference between groups in observations on the root surface with remaining periodontal ligament. From the above results, it was concluded that periodontal tissue culture of teeth with root planed surface and remaining periodontal ligament could reduce the extent of epithelium downgrowth and increase connective tissue adhesion on the root planed surface, as well as minimize damage to remaining periodontal ligament, after transplantation of teeth.
12

Iwayama, Tomoaki, Hiromi Sakashita, Masahide Takedachi, and Shinya Murakami. "Periodontal tissue stem cells and mesenchymal stem cells in the periodontal ligament." Japanese Dental Science Review 58 (November 2022): 172–78. http://dx.doi.org/10.1016/j.jdsr.2022.04.001.

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13

Adel, Ghadeer M., Ahmed A. Khalil, and Ahmed A. Moustafa. "Stem Cell with a Peri-implant Defects." NeuroQuantology 20, no. 4 (April 30, 2022): 466–68. http://dx.doi.org/10.14704/nq.2022.20.4.nq22288.

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Periodontal regeneration aims are restoring of the destructed bone, cementum and periodontal ligament. The new strategies of regeneration is very challenging, one of these strategies is tissue engineering, including stem cells and it's considered very promising solution. This paper aims to review the use of stem cells for the treatment of peri-implant defects. Nowadays, many types of mesenchymal stem cells (MSCs) have the ability of periodontal regeneration in animal studies. The bone marrow MSCs (BMMSCs), dental pulp stem cell (DPSC), periodontal ligament stem cells (PDLSCs), and gingival mesenchymal stem cells (GMSCs) are the most types that give very promising results in animal models.
14

Pejcic, A., D. Kojovic, D. Mirkovic, and I. Minic. "Stem Cells for Periodontal Regeneration." Balkan Journal of Medical Genetics 16, no. 1 (June 1, 2013): 7–11. http://dx.doi.org/10.2478/bjmg-2013-0012.

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Abstract Periodontal regeneration is considered to be biologically possible but clinically unpredictable. In periodontitis, inflammation manifests clinically as loss of supporting periodontal tissues and regeneration of damaged tissue is the main goal of treatment. For decades, periodontists have sought to repair the damage through a variety of surgical procedures, and use of grafting materials and growth factors, and of barrier membranes. Reports have emerged that demonstrate which populations of adult stem cells reside in the periodontal ligaments of humans and other animals. This opens the way for new cell-based therapies for perio-dontal regeneration. This review provides an overview of adult human stem cells and their potential use in perio-dontal regeneration.
15

Sivaram G, Dr, and Dr R. Shri Nandhini Devi. "Stem Cells in Periodontal Regeneration." IOSR Journal of Dental and Medical Sciences 13, no. 9 (2014): 31–40. http://dx.doi.org/10.9790/0853-13963140.

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16

Bartold, P. Mark, Songtao Shi, and Stan Gronthos. "Stem cells and periodontal regeneration." Periodontology 2000 40, no. 1 (February 2006): 164–72. http://dx.doi.org/10.1111/j.1600-0757.2005.00139.x.

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17

Lin, N.-H., S. Gronthos, and PM Bartold. "Stem cells and periodontal regeneration." Australian Dental Journal 53, no. 2 (June 2008): 108–21. http://dx.doi.org/10.1111/j.1834-7819.2008.00019.x.

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18

Lund, Amy E. "PERIODONTAL LIGAMENT STEM CELLS ISOLATED." Journal of the American Dental Association 135, no. 9 (September 2004): 1236. http://dx.doi.org/10.14219/jada.archive.2004.0393.

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19

Sudhakar, Uma, JRanjit Kumar, and MSatya Narayana. "Stem Cells in Periodontal Therapy." SRM Journal of Research in Dental Sciences 3, no. 2 (2012): 145. http://dx.doi.org/10.4103/0976-433x.128064.

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20

Aukhil, I., E. Pettersson, and C. Suggs. "Periodontal Wound Healing in the Absence of Periodontal Ligament Cells." Journal of Periodontology 58, no. 2 (February 1987): 71–77. http://dx.doi.org/10.1902/jop.1987.58.2.71.

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21

Nagata, Mizuki, Kengo Iwasaki, Keiko Akazawa, Motohiro Komaki, Naoki Yokoyama, Yuichi Izumi, and Ikuo Morita. "Conditioned Medium from Periodontal Ligament Stem Cells Enhances Periodontal Regeneration." Tissue Engineering Part A 23, no. 9-10 (May 2017): 367–77. http://dx.doi.org/10.1089/ten.tea.2016.0274.

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22

Chukkapalli, Sasanka S., and Tanmay P. Lele. "Periodontal cell mechanotransduction." Open Biology 8, no. 9 (September 2018): 180053. http://dx.doi.org/10.1098/rsob.180053.

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The periodontium is a structurally and functionally complex tissue that facilitates the anchorage of teeth in jaws. The periodontium consists of various cell types including stem cells, fibroblasts and epithelial cells. Cells of the periodontium are constantly exposed to mechanical stresses generated by biological processes such as the chewing motions of teeth, by flows generated by tongue motions and by forces generated by implants. Mechanical stresses modulate the function of cells in the periodontium, and may play a significant role in the development of periodontal disease. Here, we review the literature on the effect of mechanical forces on periodontal cells in health and disease with an emphasis on molecular and cellular mechanisms.
23

Seo, B. M., M. Miura, W. Sonoyama, C. Coppe, R. Stanyon, and S. Shi. "Recovery of Stem Cells from Cryopreserved Periodontal Ligament." Journal of Dental Research 84, no. 10 (October 2005): 907–12. http://dx.doi.org/10.1177/154405910508401007.

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Human post-natal stem cells possess a great potential to be utilized in stem-cell-mediated clinical therapies and tissue engineering. It is not known whether cryopreserved human tissues contain functional post-natal stem cells. In this study, we utilized human periodontal ligament to test the hypothesis that cryopreserved human periodontal ligament contains retrievable post-natal stem cells. These cryopreserved periodontal ligament stem cells maintained normal periodontal ligament stem cell characteristics, including expression of the mesenchymal stem cell surface molecule STRO-1, single-colony-strain generation, multipotential differentiation, cementum/periodontal-ligament-like tissue regeneration, and a normal diploid karyotype. Collectively, this study provides valuable evidence demonstrating a practical approach to the preservation of solid-frozen human tissues for subsequent post-natal stem cell isolation and tissue regeneration. The present study demonstrates that human post-natal stem cells can be recovered from cryopreserved human periodontal ligament, thereby providing a practical clinical approach for the utilization of frozen tissues for stem cell isolation.
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Shaikh, Muhammad Saad, Zara Shahzad, Esraa Abdulgader Tash, Omer Sefvan Janjua, Muhammad Ikram Khan, and Muhammad Sohail Zafar. "Human Umbilical Cord Mesenchymal Stem Cells: Current Literature and Role in Periodontal Regeneration." Cells 11, no. 7 (March 30, 2022): 1168. http://dx.doi.org/10.3390/cells11071168.

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Periodontal disease can cause irreversible damage to tooth-supporting tissues such as the root cementum, periodontal ligament, and alveolar bone, eventually leading to tooth loss. While standard periodontal treatments are usually helpful in reducing disease progression, they cannot repair or replace lost periodontal tissue. Periodontal regeneration has been demonstrated to be beneficial in treating intraosseous and furcation defects to varied degrees. Cell-based treatment for periodontal regeneration will become more efficient and predictable as tissue engineering and progenitor cell biology advance, surpassing the limitations of present therapeutic techniques. Stem cells are undifferentiated cells with the ability to self-renew and differentiate into several cell types when stimulated. Mesenchymal stem cells (MSCs) have been tested for periodontal regeneration in vitro and in humans, with promising results. Human umbilical cord mesenchymal stem cells (UC-MSCs) possess a great regenerative and therapeutic potential. Their added benefits comprise ease of collection, endless source of stem cells, less immunorejection, and affordability. Further, their collection does not include the concerns associated with human embryonic stem cells. The purpose of this review is to address the most recent findings about periodontal regenerative mechanisms, different stem cells accessible for periodontal regeneration, and UC-MSCs and their involvement in periodontal regeneration.
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Hendrawan, Reza Dony, Chiquita Prahasanti, Irma Josefina Savitri, and Padmini Hari. "Induced pluripotent stem cells in periodontal reconstructive therapy: A narrative review of pre-clinical studies." Dental Journal 56, no. 4 (October 24, 2023): 280–86. http://dx.doi.org/10.20473/j.djmkg.v56.i4.p280-286.

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Background: Regenerative periodontal surgical therapy faces significant challenges due to the limited ability of the body to regenerate damaged periodontal tissue. One of the primary goals in regenerative periodontal therapy is regaining periodontal tissue attachment after destruction by periodontal disease. Currently, stem cells, harnessing three pivotal components—cells, biomaterials, and growth factors—are widely used in periodontal regeneration. Stem cells can be obtained from various sources, either by isolating cells from bone marrow, teeth, and muscles or through the somatic cell programming method (reprogramming) known as induced pluripotent stem cells (iPSCs). Purpose: This review aims to describe the potential use of iPSCs in the treatment of periodontal defects. Review: Search strategies were developed using the PubMed, LILACS, Scielo, and Wiley online databases during the period of 2012–2022. Ten articles met the inclusion criteria. iPSCs were obtained by inducing somatic cells from both dental and non-dental sources with factors Oct3/4, Sox2, Klf4, and c-Myc. Periodontal tissue regeneration procedures can be augmented with iPSCs. Unlike tooth-based stem cells, iPSCs offer several advantages, such as unlimited cell sources and the capability to differentiate into any cell type, including periodontal tissue. The potential of iPSCs extends to correcting periodontal bone defects and forming new periodontal tissues, such as alveolar bone, cementum, and periodontal ligament. However, iPSCs do have limitations, including the need for clinical trials, cell programming production facilities, and optimization of differentiated-cell functionality. Conclusion: The combined use of iPSCs in cell-based tissue engineering holds vast potential for future periodontal treatment strategies.
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Gigras, Surabhi, Sudhir R. Patil, Veena HR, and Sneha Dani. "Gingival crevicular fluid level of soluble triggering recep-tor expressed on myeloid cells-1(strem-1) in periodontal health and disease: a case-control study." International Journal of Dental Research 5, no. 2 (June 3, 2017): 83. http://dx.doi.org/10.14419/ijdr.v5i2.7689.

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Background: The Triggering Receptor Expressed On Myeloid Cells-1(TREM-1) is a cell-surface receptor of the immunoglobulin superfamily and found to be involved in the amplification of the inflammatory response to various microbial infections, including periodontal diseases.Objectives: The present study was designed to examine gingivalcrevicular fluid(GCF) levels of soluble TREM-1 (sTREM-1) levels in periodontal health and disease as well as evaluate the effect of scaling and/or root planing on the same.Methods: Based on gingival index, probing pocket depth, clinical attachment level, and radiologic parameters (bone loss), 45 subjects were initially divided into three groups- Group, I (Periodontally healthy), Group II (Gingivitis) and Group III (Chronic Periodontitis).From each of the subjects, GCF sample was collected at baseline and scaling and/or root planing was instituted in group II and group III patients. GCF samples were subsequently collected at eight-week interval. Levels of sTREM-1 in collected GCF samples were estimated using enzyme-linked immunosorbent assay.Results: The lowest GCF levels of sTREM-1 were found in periodontal health (69.50±1.8pg/ml) followed by gingivitis (257.17±79pg/ml) and chronic periodontitis (3658.14±55pg/ml) in increasing order, suggesting that levels of sTREM-1 in crevicular fluid increased with the severity of periodontal disease. sTREM-1 levels decreased significantly from baseline to the end of 8 weeks following non-surgical periodontal therapy.Conclusion: Increased GCF levels of sTREM-1 from periodontal health to disease strengthen its association with periodontal status.
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Garna, Devy, Manmeet Kaur, Francis J. Hughes, and Mandeep Ghuman. "Comparison of the Expression of Periodontal Markers in Dental and Bone Marrow-derived Mesenchymal Stem Cells." Open Dentistry Journal 14, no. 1 (May 23, 2020): 196–202. http://dx.doi.org/10.2174/1874210602014010196.

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Background: Periodontal ligament stem cells are a source of mesenchymal stem cells, but it is unclear whether their phenotype is distinct from mesenchymal stem cells derived from different tissues, such as those derived from bone marrow. Objective: To investigate the expression of the putative PDL markers asporin, periostin, nestin and cementum protein 1, by periodontal ligament stem cells both constitutively and during osteogenic differentiation when compared to bone marrow-derived mesenchymal stem cells, and dental pulp stem cells. Methods: The primary human periodontal ligament, bone marrow, and dental pulp stem cells, and osteoblasts from different donors were cultured in vitro. The expression of periodontal marker associated genes during osteogenic induction was tested by qRT-PCR and immunofluorescence staining. Results: Asporin expression was detected in periodontal ligament stem cells and increased markedly during the time in culture (upregulated x53 fold at 21 days post-induction). During osteogenic differentiation, asporin expression significantly decreased in periodontal ligament cells whereas periostin significantly decreased in dental pulp cells. Periostin expression was absent in osteoblasts, but expression gradually increased in all other cells with time in culture. Nestin expression was mainly seen in the periodontal ligament and dental pulp cells and was largely absent in osteoblasts and bone marrow cells. Cementum protein-1 was most highly expressed in bone marrow cells and osteoblasts following osteogenic induction. Conclusions: The results provide further evidence that periodontal ligament-derived and bone marrow derived mesenchymal stem cells are phenotypically distinct. Periodontal markers are also expressed in dental pulp stem cells.
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Bhatt, Akanksha, Aarati Nayak, K. Satya, and Sachita Naik. "Cells-Aren’t They Stressed Too?" RGUHS Journal of Dental Sciences 14, no. 3 (2022): 25–27. http://dx.doi.org/10.26715/rjds.14_3_5.

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Periodontal disease is an infectious disease caused by several local and systemic risk factors. Stress has been identified as one of the risk factors which influences the progression of periodontal disease. Stress affects a human being as a whole, by inducing multiple changes at the cellular level. This communication focuses on stress at the cellular level, its effect on periodontal disease, and its management. We aim to present the role of naturally available resources and their potential in stress management. These help in maintaining a healthy body and mind, and thereby pave a way for a healthy, stress-free life.
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Ivanov, Alexey A., Tamara I. Danilova, Alla V. Kuznetsova, Olga P. Popova, and Oleg O. Yanushevich. "Decellularized Matrix Induced Spontaneous Odontogenic and Osteogenic Differentiation in Periodontal Cells." Biomolecules 13, no. 1 (January 6, 2023): 122. http://dx.doi.org/10.3390/biom13010122.

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The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells.
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Khodorovskyi, George, Lyubov Panina, and Tetiana Shchurko. "HORMONE-ASSOCIATED METABOLIC DISORDERS OF THE ORAL CAVITY ORGANS IN WOMEN OF REPRODUCTIVE AGE." Problems of Endocrine Pathology 78, no. 4 (December 3, 2021): 127–34. http://dx.doi.org/10.21856/j-pep.2021.4.17.

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There is emerging evidence of a possible relationship between the oral cavity and reproductive organs. Recent studies suggest these functional relations. The aim of this review was to synthesize the available evidence on this relationship. Clinical observation established that sex hormones enhance gingival inflammation in periodontal healthy women during pregnancy and that periodontal condition is associated with variation of sex hormones in blood. Estrogen regulates DNA synthesis in human gingival epithelial cells and periodontal ligament, estrogen reduces down regulation of cytokines. Estrogen and progesterone affect the periodontium via appropriate receptors (estrogen receptor and progesterone receptor). They are localized in human periodontium, demonstrating that periodontal tissues are the target tissues for these hormones. Testosterone receptors are found in the periodontal tissues. It inhibits prostaglandin secretion and reduces interleukin production. At the same time testosterone stimulates osteoblast proliferation and differentiation, also enhances matrix synthesis by fibroblast, osteoblasts, and periodontal ligament. The role of testosterone in the formation of teeth is demonstrated in the paper. In females and males, in saliva there are sex steroid hormones. The study examined the entry mode of hormones into saliva. The results suggest that lipid soluble unconjugated steroids (estriol, testosterone, progesterone) enter saliva via intracellular route; the conjugated steroids (lipid insoluble (dehydroepiandrosterone, conjugated estrogens)) enter via the ‘tight junctions’ (infiltrations through the tight junctions between the acinar cells). Recent evidence indicates that organs of the oral cavity (salivary glands, periodontal tissues, oral epithelial cells mucus) produce ghrelin-hormone which affects organs of the reproductive system directly or indirectly via hypothalamic-pituitary-gonadal axis. In all these organs, there is an appropriate receptor. In conclusion, the organs of oral cavity and organs of reproductive system are functionally linked by sex steroid hormones and ghrelin, besides that periodont can influence ovaries by neuro-reflectory link.
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Rath-Deschner, Birgit, Andressa Vilas Boas Nogueira, Svenja Memmert, Marjan Nokhbehsaim, Joni Augusto Cirelli, Sigrun Eick, Nicolai Miosge, et al. "Regulation of Anti-Apoptotic SOD2 and BIRC3 in Periodontal Cells and Tissues." International Journal of Molecular Sciences 22, no. 2 (January 8, 2021): 591. http://dx.doi.org/10.3390/ijms22020591.

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The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.
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Rath-Deschner, Birgit, Andressa Vilas Boas Nogueira, Svenja Memmert, Marjan Nokhbehsaim, Joni Augusto Cirelli, Sigrun Eick, Nicolai Miosge, et al. "Regulation of Anti-Apoptotic SOD2 and BIRC3 in Periodontal Cells and Tissues." International Journal of Molecular Sciences 22, no. 2 (January 8, 2021): 591. http://dx.doi.org/10.3390/ijms22020591.

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The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.
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Benatti, Bruno Braga, Karina Gonzales Silvério, Márcio Zaffalon Casati, Enílson Antônio Sallum, and Francisco Humberto Nociti. "Physiological features of periodontal regeneration and approaches for periodontal tissue engineering utilizing periodontal ligament cells." Journal of Bioscience and Bioengineering 103, no. 1 (January 2007): 1–6. http://dx.doi.org/10.1263/jbb.103.1.

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34

Ohsugi, Yujin, Hiromi Niimi, Tsuyoshi Shimohira, Masahiro Hatasa, Sayaka Katagiri, Akira Aoki, and Takanori Iwata. "In Vitro Cytological Responses against Laser Photobiomodulation for Periodontal Regeneration." International Journal of Molecular Sciences 21, no. 23 (November 26, 2020): 9002. http://dx.doi.org/10.3390/ijms21239002.

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Periodontal disease is a chronic inflammatory disease caused by periodontal bacteria. Recently, periodontal phototherapy, treatment using various types of lasers, has attracted attention. Photobiomodulation, the biological effect of low-power laser irradiation, has been widely studied. Although many types of lasers are applied in periodontal phototherapy, molecular biological effects of laser irradiation on cells in periodontal tissues are unclear. Here, we have summarized the molecular biological effects of diode, Nd:YAG, Er:YAG, Er,Cr:YSGG, and CO2 lasers irradiation on cells in periodontal tissues. Photobiomodulation by laser irradiation enhanced cell proliferation and calcification in osteoblasts with altering gene expression. Positive effects were observed in fibroblasts on the proliferation, migration, and secretion of chemokines/cytokines. Laser irradiation suppressed gene expression related to inflammation in osteoblasts, fibroblasts, human periodontal ligament cells (hPDLCs), and endothelial cells. Furthermore, recent studies have revealed that laser irradiation affects cell differentiation in hPDLCs and stem cells. Additionally, some studies have also investigated the effects of laser irradiation on endothelial cells, cementoblasts, epithelial cells, osteoclasts, and osteocytes. The appropriate irradiation power was different for each laser apparatus and targeted cells. Thus, through this review, we tried to shed light on basic research that would ultimately lead to clinical application of periodontal phototherapy in the future.
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Popovici, Ramona, Raluca Ceausu, Anca Cimpean, Talpos Serban, Marius Raica, and Pusa Gaje. "Mast cells as key players in periodontal disease." Archives of Biological Sciences 66, no. 2 (2014): 801–9. http://dx.doi.org/10.2298/abs1402801p.

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Mast cell (MC) active mediators promote inflammation through changes induced in the connective tissue components of human gingiva. The aim of this study was to evaluate the distribution, mast cell density and their relationship with the degree of inflammatory infiltrate in gingiva from patients with periodontal disease. Thirty-nine cases with periodontal disease and 12 cases without significant changes to the gingival mucosa were investigated. MCs were identified on paraffin-embedded specimens by immunohistochemistry using anti-mast cell tryptase. The inflammatory infiltrate was scored from 0 to 3, and the MCs were counted using the hotspot method. Intraepithelial MCs were scored from 0 to 2. We found a significant increase of mast cell density in cases with mild and moderate inflammatory changes, and a slight decrease in patients with severe periodontal disease. We noticed a higher degranulation rate in patients with periodontal disease compared to those with healthy mucosa. Intraepithelial MCs were found in cases with periodontal disease only and were correlated with the severity of the inflammatory lesion. MCs are important cellular components of the early stages of periodontal disease. Contrary to other studies, we found that MC density and activation increases with moderate inflammation but decreases in severe inflammatory lesions. Our data suggest that MCs are key players in the progression of inflammatory lesions of the gingiva. In advanced-stage periodontal disease, intraepithelial MCs apparently play an important role, although their biological significance remains to be fully understood.
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Nuñez, J., S. Sanz-Blasco, F. Vignoletti, F. Muñoz, H. Arzate, C. Villalobos, L. Nuñez, R. G. Caffesse, and M. Sanz. "Periodontal regeneration following implantation of cementum and periodontal ligament-derived cells." Journal of Periodontal Research 47, no. 1 (September 12, 2011): 33–44. http://dx.doi.org/10.1111/j.1600-0765.2011.01402.x.

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37

Han, Nannan, Yitong Liu, Juan Du, Junji Xu, Lijia Guo, and Yi Liu. "Regulation of the Host Immune Microenvironment in Periodontitis and Periodontal Bone Remodeling." International Journal of Molecular Sciences 24, no. 4 (February 5, 2023): 3158. http://dx.doi.org/10.3390/ijms24043158.

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The periodontal immune microenvironment is a delicate regulatory system that involves a variety of host immune cells including neutrophils, macrophages, T cells, dendritic cells and mesenchymal stem cells. The dysfunction or overactivation of any kind of local cells, and eventually the imbalance of the entire molecular regulatory network, leads to periodontal inflammation and tissue destruction. In this review, the basic characteristics of various host cells in the periodontal immune microenvironment and the regulatory network mechanism of host cells involved in the pathogenesis of periodontitis and periodontal bone remodeling are summarized, with emphasis on the immune regulatory network that regulates the periodontal microenvironment and maintains a dynamic balance. Future strategies for the clinical treatment of periodontitis and periodontal tissue regeneration need to develop new targeted synergistic drugs and/or novel technologies to clarify the regulatory mechanism of the local microenvironment. This review aims to provide clues and a theoretical basis for future research in this field.
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Cho, Young-Dan, Kyoung-Hwa Kim, Hyun-Mo Ryoo, Yong-Moo Lee, Young Ku, and Yang-Jo Seol. "Recent Advances of Useful Cell Sources in the Periodontal Regeneration." Current Stem Cell Research & Therapy 14, no. 1 (January 14, 2019): 3–8. http://dx.doi.org/10.2174/1574888x13666180816113456.

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Background: Periodontitis is an inflammatory disease that can result in destruction of the tooth attachment apparatus. Therefore, periodontal tissue regeneration is currently an important focus of research in the field. Approaches using stem cells and reprogrammed cells, such as induced pluripotent stem cells (iPSCs) or trans-differentiated cells, represent the cutting edge in periodontal regeneration, and have led to many trials for their clinical application. Objectives and Results: In this review, we consider all available stem cell sources, methods to obtain the cells, their capability to differentiate into the desired cells, and the extent of their utilization in periodontal regeneration. In addition, we introduce the new concepts of using iPSCs and transdifferentiated cells for periodontal regeneration. Finally, we discuss the promise of tissue engineering for improving cell therapy outcomes for periodontal regeneration. Conclusions: Despite their limitations, iPSCs and trans-differentiated cells may be promising cell sources for periodontal tissue regeneration. Further collaborative investigation is required for the effective and safe application of these cells in combination with tissue engineering elements, like scaffolds and biosignals.
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Wang, Penglai, Wen Wang, Tengyu Geng, Yi Liu, Shaoyue Zhu, Zongxiang Liu, and Changyong Yuan. "EphrinB2 regulates osteogenic differentiation of periodontal ligament stem cells and alveolar bone defect regeneration in beagles." Journal of Tissue Engineering 10 (January 2019): 204173141989436. http://dx.doi.org/10.1177/2041731419894361.

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EphrinB2, a membrane protein regulating bone homeostasis, has been demonstrated to induce osteogenic gene expression in periodontal ligament fibroblasts. The aim of this study was to explore the effects of ephrinB2 on osteogenic differentiation of periodontal ligament stem cells and on alveolar bone regeneration in vivo. We assessed the osteogenic gene expression and osteogenic differentiation potential of ephrinB2-modified human and canine periodontal ligament stem cells, in which ephrinB2 expression was upregulated via lentiviral vector transduction. EphrinB2-modified canine periodontal ligament stem cells combined with PuraMatrix were delivered to critical-sized alveolar bone defects in beagles to evaluate bone regeneration. Results showed that ephrinB2 overexpression enhanced osteogenic gene transcription and mineral deposition in both human and canine periodontal ligament stem cells. Animal experiments confirmed that ephrinB2-modified canine periodontal ligament stem cells + PuraMatrix resulted in greater trabecular bone volume per tissue volume and trabecular thickness compared with other groups. Our study demonstrated that ephrinB2 promoted osteogenic differentiation of periodontal ligament stem cells and alveolar bone repair in beagles, highlighting its therapeutic potential for the treatment of alveolar bone damage.
40

Onizuka, Satoru, and Takanori Iwata. "Application of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets for Periodontal Regeneration." International Journal of Molecular Sciences 20, no. 11 (June 7, 2019): 2796. http://dx.doi.org/10.3390/ijms20112796.

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Periodontitis is a chronic inflammatory disorder that causes destruction of the periodontal attachment apparatus including alveolar bone, the periodontal ligament, and cementum. Dental implants have been routinely installed after extraction of periodontitis-affected teeth; however, recent studies have indicated that many dental implants are affected by peri-implantitis, which progresses rapidly because of the failure of the immune system. Therefore, there is a renewed focus on periodontal regeneration aroundnatural teeth. To regenerate periodontal tissue, many researchers and clinicians have attempted to perform periodontal regenerative therapy using materials such as bioresorbable scaffolds, growth factors, and cells. The concept of guided tissue regeneration, by which endogenous periodontal ligament- and alveolar bone-derived cells are preferentially proliferated by barrier membranes, has proved effective, and various kinds of membranes are now commercially available. Clinical studies have shown the significance of barrier membranes for periodontal regeneration; however, the technique is indicated only for relatively small infrabony defects. Cytokine therapies have also been introduced to promote periodontal regeneration, but the indications are also for small size defects. To overcome this limitation, ex vivo expanded multipotent mesenchymal stromal cells (MSCs) have been studied. In particular, periodontal ligament-derived multipotent mesenchymal stromal cells are thought to be a responsible cell source, based on both translational and clinical studies. In this review, responsible cell sources for periodontal regeneration and their clinical applications are summarized. In addition, recent transplantation strategies and perspectives about the cytotherapeutic use of stem cells for periodontal regeneration are discussed.
41

Liu, Jin, Jianping Ruan, Michael D. Weir, Ke Ren, Abraham Schneider, Ping Wang, Thomas W. Oates, Xiaofeng Chang, and Hockin H. K. Xu. "Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells." Cells 8, no. 6 (June 4, 2019): 537. http://dx.doi.org/10.3390/cells8060537.

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Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.
42

Rath-Deschner, Birgit, Svenja Memmert, Anna Damanaki, Marjan Nokhbehsaim, Sigrun Eick, Joni A. Cirelli, Werner Götz, James Deschner, Andreas Jäger, and Andressa V. B. Nogueira. "CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies." Clinical Oral Investigations 24, no. 10 (March 2, 2020): 3661–70. http://dx.doi.org/10.1007/s00784-020-03244-1.

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Abstract Objectives This study was established to investigate whether the chemokines CXCL1, CCL2, and CCL5 are produced in periodontal cells and tissues and, if so, whether their levels are regulated by microbial and/or mechanical signals. Materials and methods The chemokine expression and protein levels in gingival biopsies from patients with and without periodontitis were analyzed by RT-PCR and immunohistochemistry. The chemokines were also analyzed in gingival biopsies from rats subjected to experimental periodontitis and/or orthodontic tooth movement. Additionally, chemokine levels were determined in periodontal fibroblasts exposed to the periodontopathogen Fusobacterium nucleatum and mechanical forces by RT-PCR and ELISA. Results Higher CXCL1, CCL2, and CCL5 levels were found in human and rat gingiva from sites of periodontitis as compared with periodontally healthy sites. In the rat experimental periodontitis model, the bacteria-induced upregulation of these chemokines was significantly counteracted by orthodontic forces. In vitro, F. nucleatum caused a significant upregulation of all chemokines at 1 day. When the cells were subjected simultaneously to F. nucleatum and mechanical forces, the upregulation of chemokines was significantly inhibited. The transcriptional findings were paralleled at protein level. Conclusions This study provides original evidence in vitro and in vivo that the chemokines CXCL1, CCL2, and CCL5 are regulated by both microbial and mechanical signals in periodontal cells and tissues. Furthermore, our study revealed that biomechanical forces can counteract the stimulatory actions of F. nucleatum on these chemokines. Clinical relevance Mechanical loading might aggravate periodontal infection by compromising the recruitment of immunoinflammatory cells.
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Chandra, R. Viswa, Ganesh Chandra Jagetia, and K. Mahalinga Bhat. "The Attachment of V79 and Human Periodontal Ligament Fibroblasts on Periodontally Involved Root Surfaces Following Treatment with EDTA, Citric Acid, or Tetracycline HCL: An SEM in vitro Study." Journal of Contemporary Dental Practice 7, no. 1 (2006): 35–43. http://dx.doi.org/10.5005/jcdp-7-1-35.

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Abstract Objective The present in vitro study has been designed to establish and compare the effects of citric acid, EDTA, and tetracycline HCl on human periodontally diseased roots on the structure, attachment, and orientation of V79 (primary Chinese hamster lung fibroblasts) cells and human periodontal ligament fibroblasts (HPDL). Materials and Methods Commercially availableV79 cells and HPDL derived from healthy human third molars were used in this study. These fibroblasts were left in solution for seven days in order to attain confluence. Forty single-rooted teeth were obtained from patients diagnosed with periodontitis. The crown part was removed under constant irrigation and the root was split vertically into two equal halves, thus, yielding 80 specimens. Following scaling and root planing, the specimens were washed with phosphate buffered saline (PBS) and kept in 50 μg/ml gentamycin sulphate solution for 24 hours. The root pieces were then treated as follows: citric acid at pH 1, 24% EDTA, or with a 10% solution of tetracycline HCl and were then placed in V79 fibroblast cultures and HPDL cultures. The specimens were harvested after four weeks and were fixed in 2.5% glutaraldehyde in PBS before preparation for scanning electron microscopy (SEM). Results The behavior of V79 cells was similar to that of human periodontal ligament cells on root conditioned surfaces. V79 and HPDL showed a healthy morphology on root surfaces treated with citric acid and EDTA and a relatively unhealthy appearance on root surfaces treated with tetracycline HCl and distilled water (control group). Conclusion The results suggest the use of citric acid and EDTA as root conditioning agents favorably affects the migration, attachment, and morphology of fibroblasts on human root surfaces, which may play a significant role in periodontal healing and regeneration. Citation Chandra RV, Jagetia GC, Bhat KM. The Attachment of V79 and Human Periodontal Ligament Fibroblasts on Periodontally Involved Root Surfaces Following Treatment with EDTA, Citric Acid, or Tetracycline HCL: An SEM in vitro Study. J Contemp Dent Pract 2006 February;(7)1:044-059.
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Chandra, R. Viswa, Ganesh Chandra Jagetia, and K. Mahalinga Bhat. "The Attachment of V79 and Human Periodontal Ligament Fibroblasts on Periodontally Involved Root Surfaces Following Treatment with EDTA, Citric Acid, or Tetracycline HCL: An SEM in vitro Study." Journal of Contemporary Dental Practice 7, no. 1 (2006): 44–59. http://dx.doi.org/10.5005/jcdp-7-1-44.

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Abstract Objective The present in vitro study has been designed to establish and compare the effects of citric acid, EDTA, and tetracycline HCl on human periodontally diseased roots on the structure, attachment, and orientation of V79 (primary Chinese hamster lung fibroblasts) cells and human periodontal ligament fibroblasts (HPDL). Materials and Methods Commercially availableV79 cells and HPDL derived from healthy human third molars were used in this study. These fibroblasts were left in solution for seven days in order to attain confluence. Forty single-rooted teeth were obtained from patients diagnosed with periodontitis. The crown part was removed under constant irrigation and the root was split vertically into two equal halves, thus, yielding 80 specimens. Following scaling and root planing, the specimens were washed with phosphate buffered saline (PBS) and kept in 50 μg/ml gentamycin sulphate solution for 24 hours. The root pieces were then treated as follows: citric acid at pH 1, 24% EDTA, or with a 10% solution of tetracycline HCl and were then placed in V79 fibroblast cultures and HPDL cultures. The specimens were harvested after four weeks and were fixed in 2.5% glutaraldehyde in PBS before preparation for scanning electron microscopy (SEM). Results The behavior of V79 cells was similar to that of human periodontal ligament cells on root conditioned surfaces. V79 and HPDL showed a healthy morphology on root surfaces treated with citric acid and EDTA and a relatively unhealthy appearance on root surfaces treated with tetracycline HCl and distilled water (control group). Conclusion The results suggest the use of citric acid and EDTA as root conditioning agents favorably affects the migration, attachment, and morphology of fibroblasts on human root surfaces, which may play a significant role in periodontal healing and regeneration. Citation Chandra RV, Jagetia GC, Bhat KM. The Attachment of V79 and Human Periodontal Ligament Fibroblasts on Periodontally Involved Root Surfaces Following Treatment with EDTA, Citric Acid, or Tetracycline HCL: An SEM in vitro Study. J Contemp Dent Pract 2006 February;(7)1:044-059.
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Okada, H., Y. Shimabukuro, Y. Kassai, H. Ito, T. Matsuo, S. Ebisu, and Y. Harada. "The Function of Gingival Lymphocytes on the Establishment of Human Periodontitis." Advances in Dental Research 2, no. 2 (November 1988): 364–67. http://dx.doi.org/10.1177/08959374880020022801.

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Human periodontitis has been confirmed to be an IgG plasma cell-rich lesion. However, we also detected many T cells, both CD4-positive and CD8-positive cells, in periodontal lesions. Some of these T cells expressed HLA-DR (la-like) antigen on their surfaces, and the proportion of HLA-DR+ cells was approximately equal in both CD4+ and CD8+ cell populations (Okada et al., 1983, 1984). Consequently, both helper and suppressor T cells were believed to participate in the establishment of periodontal lesions. On the other hand, B cells were thought to be activated polyclonally in periodontal lesions, because a variety of periodontal florae possessed polyclonal B-cell-activating activity. We demonstrated that Actinomyces viscosus T14V stimulated mouse spleen B cells polyclonally and induced many IgM-producing cells but few IgG-producing cells. Moreover, IgG-producing cells were differentiated from only surface IgG-positive B cells but not from surface IgG-negative B cells-namely, surface IgM- or IgA-positive B cells (Harada et al., 1988). These results suggested that memory B cells, which had already been primed with appropriate antigens, might migrate into periodontal lesions, and then be activated polyclonally and develop into IgG-producing cells. The periodontal lesion could, therefore, be induced by the interactions of immunoregulatory mechanisms of T cells and polyclonal B cell activity of periodontal florae. In fact, L3T4-positive T cells (helper-inducer T cells) enhanced IgG synthesis of mouse spleen B cells which had been activated with T-independent B cell activators such as LPS and A. viscosus preparations (Okada et al., 1987; Ito et al., 1988). We hypothesized from the above results that autoreactive T cells recognized the increasing self-MHC class II(Ia) antigen on B cells which had been activated with polyclonal B cell activators, and then produced soluble factors, which could enhance IgG synthesis of these B cells. Autoreactive T cells as well as PBAs, thus, may play an important role in the establishment of the IgG plasma cell-rich periodontal lesion.
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DuBois, William T., Jeffery Edmondson, Stephen B. Milam, William B. Winborn, Robert Hay, David L. Carnes, Kenneth S. Kornman, and Robert J. Klebe. "Monoclonal Antibodies to Periodontal Ligament Cells." Journal of Periodontology 62, no. 3 (March 1991): 190–96. http://dx.doi.org/10.1902/jop.1991.62.3.190.

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Lin, Ni-Hung, Stan Gronthos, and P. Mark Bartold. "Stem cells and future periodontal regeneration." Periodontology 2000 51, no. 1 (October 2009): 239–51. http://dx.doi.org/10.1111/j.1600-0757.2009.00303.x.

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Gemmell, E., C. L. Carter, and G. J. Seymour. "Mast Cells in Human Periodontal Disease." Journal of Dental Research 83, no. 5 (May 2004): 384–87. http://dx.doi.org/10.1177/154405910408300506.

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Recently, mast cells have been shown to produce cytokines which can direct the development of T-cell subsets. The aim of the present study was to determine the relationship between mast cells and the Th1/Th2 response in human periodontal disease. Tryptase+ mast cell numbers were decreased in chronic periodontitis tissues compared with healthy/gingivitis lesions. Lower numbers of c-kit+ cells, which remained constant regardless of clinical status, indicate that there may be no increased migration of mast cells into periodontal disease lesions. While there were no differences in IgG2+ or IgG4+ cell numbers in healthy/gingivitis samples, there was an increase in IgG4+ cells compared with IgG2+ cells in periodontitis lesions, numbers increasing with disease severity. This suggests a predominance of Th2 cells in periodontitis, although mast cells may not be the source of Th2-inducing cytokines.
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Roguljic, H., B. G. Matthews, W. Yang, H. Cvija, M. Mina, and I. Kalajzic. "In vivoIdentification of Periodontal Progenitor Cells." Journal of Dental Research 92, no. 8 (June 4, 2013): 709–15. http://dx.doi.org/10.1177/0022034513493434.

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Ivanovski, S., S. Gronthos, S. Shi, and PM Bartold. "Stem cells in the periodontal ligament." Oral Diseases 12, no. 4 (July 2006): 358–63. http://dx.doi.org/10.1111/j.1601-0825.2006.01253.x.

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