Gene therapy for temporomandibular joint osteoarthritis

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12557169
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: 補綴理工系歯学
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: KUBOKI Takuo Okayama University Graduate School of Medicine and Dentistry Associate Professor, 大学院・医歯学総合研究科, 助教授 (00225195)
• Co-Investigator(Kenkyū-buntansha): NAKANISHI Tohru Okayama University Graduate School of Medicine and Dentistry Associate Professor, 大学院・医歯学総合研究科, 助教授 (30243463) ; TAKIGAWA Masaharu Okayama University Graduate School of Medicine and Dentistry Professor, 大学院・医歯学総合研究科, 教授 (20112063) ; FUJISAWA Takuo Okayama University Graduate School of Medicine and Dentistry Research Associate, 大学院・医歯学総合研究科, 助手 (20325096) ; KASAI Teruo Okayama University Dental Hospital Research Associate, 大学院・医歯学総合研究科, 助教授 (00335613) ; YATANI Hirofumi Okayama University Graduate School of Medicine and Dentistry Professor, 大学院・医歯学総合研究科, 教授 (80174530)
• Project Period (FY): 2000 – 2002
• Keywords: Osteoarthritis / Mechanical stress / Articular cartilage / Gene therapy / Adenovirus / Chondrocyte

Research Abstract

The purposes of this research are to clarify the mechanism of cartilage degradation in osteoarthritis (OA) and to investigate the possibility of gene therapy for articular cartlige restoration using connective tissue growth fector (CTGF).
First, we establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive forced jaw opening (RFJO) 3 hours/day for 5 days was applied. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the RFJO period. These results suggest the RFJO protocol without any surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.
Second, we investigated the effects of CTGF/Hcs24 transduced by recombinant adenoviruses on the rabbit articular cartilage (RAC) cells in vitro. When RAC cells were infected with adenoviruses caontaining the CTGF/Hcs24 gene, RAC cells expressed CTGF/Hcs24 mRNA and produced CTGF/Hcs24 protein. RAC cells synthesized more proteoglycan than the control cells.

Research Products

• [Publications] T.Kuboki et al.: "CTGF/Hcs24, a hypertrophic chondrocytes specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes"J Cellular Physiol.. 192. 55-63 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T Kuboki et al.: "Soluble tumor necrosis factor receptors are up-regulated in synovial fluids from osteoarthritic temporomandibular joints"Archs Oral Biol. (in press). (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T Fujisawa et al.: "A repetitive mouth opening induced osteoarthritis-like lesion in rabbit temporomandibular joint"J Dent Res. (in press). (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T. Nishida, S. Kubota, T. Nakanishi, T. Kuboki, G. Yoshimichi, S. Kondo, M. Takigawa: "CTGF/Hcs24, a hypertrpphic chondrocytes specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes"J Cellular Physiol.. 192(1). 55-63 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] J. Uehara, T. Kuboki, T. Fujisawa, S. Kojima, K. Maekawa, H. Yatani: "Soluble tumor necrosis factor receptors are up-regulated in synovial fluids from osteoarthritic temporomandibular joints, preliminarily accepted"Archs Oral Biol.. (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Fujisawa, T. Kuboki, T. Kasai, W. Sonoyama, S. Kojima, J. Uehara, C. Komori, H. Yatani, T. Hattori, M. Takigawa: "A repetitive mouth opening induced osteoarthritis-like lesion in rabbit temporomandibular joint, preliminarily accepted"J Dent Res.. (2003)
  • Description: 「研究成果報告書概要(欧文)」より