Most of our bones are produced by endochondral ossification, the replacement of cartilage by bone. The individual steps of this process –chondrocyte proliferation followed by apoptosis, remodelling of the cartilage extracellular matrix (ECM), angiogenesis and osteoblast recruitment –are well characterised. Now Stickens and co-workers identify ECM remodelling as the dominant rate-limiting process in bone morphogenesis by examining how disruption of ECM remodelling affects bone development in mice (see p. ). They report that inactivation of Mmp13, which encodes collagenase 3, causes abnormal skeletal growth plate development. They also use mice lacking both Mmp13 and Mmp9 to show that these enzymes synergistically degrade collagen type II and aggrecan during bone development. These and other results lead the researchers to conclude that proper endochondral ossification requires not only the assembly of cartilage collagens but also their degradation.
