Bone morphogenetic proteins (BMPs) are important in many developmental processes but were originally identified as factors inducing the ectopic formation of bone and cartilage. On p. 229, Nakayama and colleagues bring the BMP story full circle by identifying a new chordin-like secreted BMP inhibitor, CHL2, that is expressed almost exclusively in the chondrocytes of developing joint cartilage. The researchers show that recombinant mouse CHL2 (mCHL2) interacts directly with several BMPs and inhibits many BMP-dependent processes in vitro. In particular, the addition of exogenous mCHL2 to a chondrogenic culture system reduces cartilage matrix deposition and mineralisation. The findings indicate that CHL2 may regulate the formation and maintenance of articular cartilage. Finally, CHL2expression is upregulated in middle zone chondrocytes of osteoarthritic joint cartilage; thus, this novel BMP inhibitor could also be involved in the pathogenesis of degenerative joint disease.

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