Overexpression of active TGF-beta-1 in the murine knee joint: evidence forsynovial-layer-dependent chondro-osteophyte formation

Objective: To investigate the impact of a prolonged and constant active TGF -beta expression by the synovial lining cells on cartilage and ligamentous joint structures in vivo. Design: An adenoviral vector (AdTGF-beta1(223.225)) was used for the overex pression of active TGF-beta1 in knee joints of C57B1/6 mice. Results: It was found that physiological relevant levels of active TGF-beta 1 produced by the synovial lining layer resulted in histopathological chang es: hyperplasia of synovium and chondro-osteophyte formation at the so-call ed chondro-synovial junctions. No histological changes were seen after intr a-articular injection of an empty control vector (AdDL70-3) or by overexpre ssion of latent TGF-beta1 (AdTGF-beta1). The predominant site of TGF-beta p roduction in osteoarthritis (OA) and rheumatoid arthritis (RA) is the synov ial lining layer. To address the question whether the TGF-beta -induced cha nges were related to the expression site in the synovial lining, the synovi al lining layer was depleted by local treatment with liposomes encapsulatin g clodronate. Depletion of the lining resulted in a dramatic change of TGF- beta1-induced pathology: markedly reduced chondro-osteophyte formation and increased accumulation of extracellular matrix in the synovium. Conclusion: This study shows that overexpression of active TGF-beta1 in the knee joint results in OA-like changes and suggests the synovial lining cel ls contribute to the chondro-osteophyte formation. (C) 2001 OsteoArthritis Research Society International.