Bone morphogenetic proteins and articular cartilage: To serve and protect or a wolf in sheep clothing's?
OBJECTIVE
Alterations in chondrocyte differentiation and matrix remodeling play a central role in osteoarthritis (OA). Chondrocyte differentiation and remodeling are amongst others regulated by the so-called Bone Morphogenetic Proteins (BMPs). Although BMPs are considered protective for articular cartilage these factors can also be involved in chondrocyte hypertrophy and matrix degradation. This review is focused on these opposed roles of BMPs in OA development and progression.


METHODS
Peer reviewed publications published prior to August 2009 were searched in the Pubmed database. Articles that were relevant for the role of endogenous BMPs in OA were selected. Since good quality reviews on the application of BMP supplementation in cartilage tissue engineering have been described this subject has not been covered in this review.


RESULTS
BMPs can stimulate both chondrocyte matrix synthesis and chondrocyte terminal differentiation. The latter results in elevated matrix metalloproteinase-13 (MMP-13) production. Stimulation of matrix synthesis will be protective for cartilage while elevated MMP-13 activity will drive matrix degradation. What action of BMPs is dominant in OA is not yet elucidated and their role might be different in patient subgroups.


CONCLUSIONS
BMPs can be protective for articular cartilage but can, due to their effect on chondrocyte differentiation, have harmful effects on articular cartilage and contribute to OA progression.
van der Kraan
P M
PM
Experimental Rheumatology & Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. P.vanderkraan@reuma.umcn.nl
Blaney Davidson
E N
EN
van den Berg
W B
WB
D019485:Bone Morphogenetic Proteins / Q000502:physiology* / Q000627:therapeutic use; D002358:Cartilage, Articular / Q000473:pathology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy / Q000503:physiopathology*
D019485:Bone Morphogenetic Proteins