Inhibition of transforming growth factor-β in osteoarthritis. Discrepancy with reduced TGFβ signaling in normal joints.

Objective: Transforming growth factor-β (TGFβ) is a pleiotropic cytokine that is central in the regulation of joint health and disease. Inhibition of TGFβ activity/signaling in experimental osteoarthritis (OA) has been performed to modulate OA severity and progression. In this narrative review we discuss the potential reasons for the variable results of TGFβ inhibition in these models. Design: A literature study was performed using the search terms; experimental osteoarthritis and TGFβ. Papers were selected that describe the effect TGFβ activity/signaling inhibition on experimental OA. Based on the selected papers a narrative review has been written about the potential therapeutic role of TGFβ inhibition in OA and potential causes for its variable effects are discussed. Results: Inhibition of TGFβ activity in experimental models of OA does not result in either straightforward protection or deleterious effects. More than half of the studies (13/19), but not all, report that inhibition of TGFβ in experimental OA reduces OA severity. This is in contrast with the protective role of TGFβ in healthy joints. Conclusions: The effect of TGFβ inhibition on joint damage in experimental OA is variable. Most likely this is a consequence of the changing function of TGFβ in normal and OA joints. As a result, the overall outcome of TGFβ modulation in OA will be unpredictable. To develop OA therapies based on modulation of TGFβ activity specific protective and damaging signaling routes should be identified and tools developed to block the damaging ones.