Abstract
This study evaluated the ability of human osteoprotegerin gene-modified autologous periodontal ligament cells (PDLCs) in combination with cell transplantation to promote periodontal regeneration in beagle dogs. Adenovirus Ad5-hOPG-EGFP-transfected PDLCs and BME-10X collagen membranes were fabricated and used for periodontal repair. Buccal periodontal defects (mesiodistal width × depth: 5 × 5 mm) were created on the second, third, and fourth mandibular premolars in six normal beagle dogs, and the defects were histologically and histomorphometrically assessed for periodontal regeneration in the following four groups: (1) hOPG-PDLCs + BME-10X, (2) mock-PDLCs + BME-10X, (3) PDLCs + BME-10X, and (4) BME-10X. The radiographic and histological results suggested that hOPG-PDLCs significantly promoted periodontal defect repair. This study demonstrates the potential of hOPG-modified PDLCs for periodontal tissue regeneration.
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Beck JD, Offenbacher S, Williams R, Gibbs P, Garcia R (1998) Periodontitis: a risk factor for coronary heart disease? Ann Periodontol 3:127–141
Belibasakis GN, Bostanci N (2012) The RANKL-OPG system in clinical periodontology. J Clin Periodontol 39:239–248
Belibasakis GN, Johansson A, Wang Y, Chen C, Kalfas S, Lerner U (2005) The cytolethal distending toxin induces receptor activator of NF-κB ligand expression in human gingival fibroblasts and periodontal ligament cells. Infect Immun 73:342–351
Bostanci N, İlgenli T, Emingil G, Afacan B, Han B, Töz H, Atilla G, Hughes FJ, Belibasakis GN (2007) Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. J Clin Periodontol 34:370–376
Chen R, Kanzaki H, Chiba M, Nishimura M, Kanzaki R, Igarashi K (2008) Local osteoprotegerin gene transfer to periodontal tissue inhibits lipopolysaccharide-induced alveolar bone resorption. J Periodontal Res 43:237–245
Cochran DL (2008) Inflammation and bone loss in periodontal disease. J Periodontol 79:1569–1576
Crotti T, Smith MD, Hirsch R, Soukoulis S, Weedon H, Capone M, Ahern MJ, Haynes D (2003) Receptor activator NF κB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis. J Periodontal Res 38:380–387
Dörtbudak O, Eberhardt R, Ulm M, Persson GR (2005) Periodontitis, a marker of risk in pregnancy for preterm birth. J Clin Periodontol 32:45–52
Eke P, Dye B, Wei L, Thornton-Evans G, Genco R (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res 91:914–920
Hasegawa T, Yoshimura Y, Kikuiri T, Yawaka Y, Takeyama S, Matsumoto A, Oguchi H, Shirakawa T (2002) Expression of receptor activator of NF-kappa B ligand and osteoprotegerin in culture of human periodontal ligament cells. J Periodontal Res 37:405–411
Jin Q, Cirelli JA, Park CH, Sugai JV, Taba M Jr, Kostenuik PJ, Giannobile WV (2007) RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis. J Periodontol 78:1300–1308
Kanzaki H, Chiba M, Shimizu Y, Mitani H (2001) Dual regulation of osteoclast differentiation by periodontal ligament cells through RANKL stimulation and OPG inhibition. J Dent Res 80:887–891
Lacey D, Timms E, Tan H-L, Kelley M, Dunstan C, Burgess T, Elliott R, Colombero A, Elliott G, Scully S (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176
Lacey DL, Tan HL, Lu J, Kaufman S, Van G, Qiu W, Rattan A, Scully S, Fletcher F, Juan T (2000) Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 157:435–448
Liu XY (2006) Targeting gene-virotherapy of cancer and its prosperity. Cell Res 16:879–886
Mealey BL, Rethman MP (2003) Periodontal disease and diabetes mellitus. Bidirectional relationship. Dent Today 22:107–113
Mercado F, Marshall RI, Klestov AC, Bartold PM (2000) Is there a relationship between rheumatoid arthritis and periodontal disease? J Clin Periodontol 27:267–272
Nibali L, Farias B, Vajgel A, Tu Y, Donos N (2013) Tooth loss in aggressive periodontitis: a systematic review. J Dent Res 92:868–875
Page RC, Engel LD, Narayanan AS, Clagett JA (1978) Chronic inflammatory gingival and periodontal disease. JAMA 240:545–550
Ribeiro FS, Pontes AEF, Zuza EP, da Silva VC, Lia RCC, Junior EM, Sheikh Z, Abdallah M-N, Hamdan N, Javaid M (2005) Position paper: periodontal regeneration. J Periodontol 76:1601–1622
Sasaki N, Kusano E (2006) Bone and bone related biochemical examinations. Bone and collagen related metabolites. Measurement and clinical role of OPG. Clin Calcium 16:956–962
Shiba H, Nakanishi K, Sakata M, Fujita T, Uchida Y, Kurihara H (2000) Effects of ageing on proliferative ability, and the expressions of secreted protein, acidic and rich in cysteine (SPARC) and osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human periodontal ligament cells. Mech Ageing Dev 117:69–77
Silness J, Löe H (1964) Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition. Acta Odontol 22:121–135
Takayanagi H (2005) Inflammatory bone destruction and osteoimmunology. J Periodontal Res 40:287–293
Taubman MA, Valverde P, Han X, Kawai T (2005) Immune response: the key to bone resorption in periodontal disease. J Periodontol 76:2033–2041
Teng Y-TA, Nguyen H, Gao X, Kong Y-Y, Gorczynski RM, Singh B, Ellen RP, Penninger JM (2000) Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Investig 106:R59
Villar CC, Cochran DL (2010) Regeneration of periodontal tissues: guided tissue regeneration. Dent Clin North Am 54:73–92
Yasuda H, Shima N, Nakagawa N, Mochizuki S-I, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337
Zhang D, Yang Y, Li X, Fu M (2004) The expression of osteoprotegerin and the receptor activator of nuclear factor kappa B ligand in human periodontal ligament cells cultured with and without 1α, 25-dihydroxyvitamin D. Arch Oral Biol 49:71–76
Acknowledgments
This study was supported by the International Cooperation Research and Develop Project of Nanjing Health Bureau (No. 201303051), “Six Talent Peaks” of High Level Talent Selection and Training Project of Jiangsu Province (No. 2013-SWYY-006), Research Fund for the Doctoral Program of Higher Education of China (No. 20093518110002) and Key Project of Science and Technology Bureau of Jiangsu Province (No. BL2013002).
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Jiang, S., Tang, K., Chen, B. et al. Regenerative effect of hOPG gene-modified autologous PDLs in combination with cell transplantation on periodontal defection in beagle dogs. Cytotechnology 68, 2613–2623 (2016). https://doi.org/10.1007/s10616-016-9985-y
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DOI: https://doi.org/10.1007/s10616-016-9985-y