Abstract
Objective
Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and osteophyte formation. Both transforming growth factor β (TGFβ) 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 TGFβ and BMP‐2 to OA.
Methods
Mouse knee joints injected with adenovirus (Ad‐TGFβ 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‐TGFβ 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 TGFβ 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 TGFβ‐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 TGFβ‐induced nor experimental OA–associated osteophyte formation.
Conclusion
Our findings demonstrate that the role of BMP during the onset of TGFβ‐induced and experimental OA–induced osteophyte formation is limited. The latter finding does not rule out a role of BMP during osteophyte maturation.