Tetsuya Hattori1, Masahiro Hasegawa1, Hironori Unno1, Takahiro Iino1, Fumio Fukai2, Toshimichi Yoshida3, Akihiro Sudo1. 1. Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie, Japan. 2. Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda City, Chiba, Japan. 3. Departments of Pathology & Matrix Biology, Mie University Graduate School of Medicine, Tsu City, Mie, Japan.
Abstract
OBJECTIVE: TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model. DESIGN: Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction. RESULTS: There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor. CONCLUSION: We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.
OBJECTIVE: TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model. DESIGN: Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction. RESULTS: There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor. CONCLUSION: We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.
Authors: V Krenn; L Morawietz; G-R Burmester; R W Kinne; U Mueller-Ladner; B Muller; T Haupl Journal: Histopathology Date: 2006-10 Impact factor: 5.087
Authors: N Okamura; M Hasegawa; Y Nakoshi; T Iino; A Sudo; K Imanaka-Yoshida; T Yoshida; A Uchida Journal: Osteoarthritis Cartilage Date: 2009-09-06 Impact factor: 6.576