Osteoarthritis-like changes in the murine knee joint resulting from intra-articular transforming growth factor-beta injections

Objective: To examine the impact of prolonged TGF-beta exposure on cartilag e and ligamentous joint structures in vivo, to investigate involvement of T GF-beta in osteoarthritis pathology. Methods: TGF-beta was injected into murine knee joints once or repeatedly, whereafter articular cartilage proteoglycan (PG) synthesis and content, and histological changes in knee joints were studied over a 2-month period. Results: A single injection of TGF-beta stimulated patellar cartilage PG sy nthesis for 3 weeks and PG content for 2 weeks. Triple TGF-beta injections prolonged the increase in PG content to 3 weeks. Patellar cartilage showed no histological abnormalities at 1 and 2 months after the last injection. I n contrast, 2 months after triple TGF-beta injections the superficial layer of tibial cartilage still had an increased proteoglycan content, while sev ere PG depletion was found in deeper layers of the posterior part of the la teral tibia in particular. Eventually, lesions occurred at the level of the tide-mark, exactly the site where cartilage is torn off in experimental an d spontaneous osteoarthritis in mice. Additionally, multiple TGF-beta injec tions induced formation of chondroid structures along the margins of articu lar cartilage. These chondroid structures were transformed into osteophytes via endochondral ossification. Formation of chondroid tissue was also obse rved in collateral ligaments. Conclusion: Multiple intra-articular injections of TGF-beta induce changes in articular cartilage and surrounding tissues that have strong resemblance to features of experimental and spontaneous osteoarthritis in mice, sugges ting a role for TGF-beta in the OA process. (C) 2000 OsteoArthritis Researc h Society International.