Resemblance of osteophytes in experimental osteoarthritis to transforming growth factor β-induced osteophytes

Objective. Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and osteophyte formation. Both transforming growth factor 13 (TGF beta) and bone morphogenetic protein 2 (BMP-2) can induce the formation of osteophytes during OA, but their specific role in this process is unclear. The purpose of this study was to investigate the respective contributions of TGF beta and BMP-2 to OA. Methods. Mouse knee joints injected with adenovirus (Ad-TGF beta or Ad-BMP-2) were compared histologically with knee joints from murine models of OA (joints injected with collagenase and joints from STR/Ort mice with spontaneous OA). To further investigate the role of BMP during osteophyte formation, adenovirus Ad-Gremlin was injected into knee joints that had previously been injected with Ad-TGF beta or collagenase. Results. BMP-2 induced early osteophytes, which bulged from the growth plates on the femur and grew on top of the patella, whereas TGF beta induced early osteophyte formation on the bone shaft beneath the collateral ligament on the femur as well as on top of the patella. The pattern of osteophyte formation during experimental OA closely resembled that of TGF beta-induced osteophyte formation, but differed from the pattern induced by BMP-2. Ad-Gremlin proved to be able to totally block BMP-2-induced osteophyte formation. However, blocking BMP activity inhibited neither TGF beta-induced nor experimental OA-associated osteophyte formation. Conclusion. Our findings demonstrate that the role of BMP during the onset of TGF beta-induced and experimental OA-induced osteophyte formation is limited. The latter finding does not rule out a role of BMP during osteophyte maturation.