Resemblance of osteophytes in experimental osteoarthritis to transforming growth factor beta-induced osteophytes: limited role of bone morphogenetic protein in early osteoarthritic osteophyte formation.
OBJECTIVE
Osteoarthritis (OA) is characterized by cartilage damage, synovial fibrosis, and osteophyte formation. Both transforming growth factor beta (TGFbeta) 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 TGFbeta and BMP-2 to OA.


METHODS
Mouse knee joints injected with adenovirus (Ad-TGFbeta 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-TGFbeta 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 TGFbeta 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 TGFbeta-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 TGFbeta-induced nor experimental OA-associated osteophyte formation.


CONCLUSIONS
Our findings demonstrate that the role of BMP during the onset of TGFbeta-induced and experimental OA-induced osteophyte formation is limited. The latter finding does not rule out a role of BMP during osteophyte maturation.
Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. e.blaneydavidson@reuma.umcn.nl
E N
EN
Blaney Davidson
E L
EL
Vitters
H M
HM
van Beuningen
F A J
FA
van de Loo
W B
WB
van den Berg
P M
PM
van der Kraan
D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D017364:Collagenases; D016207:Cytokines; D004195:Disease Models, Animal; D018450:Disease Progression; D007270:Injections, Intra-Articular; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D054850:Osteophyte / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017364:Collagenases; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C525719:Bmp2 protein, mouse; C113178:Grem1 protein, mouse