RECAPITULATION OF SIGNALS REGULATING EMBRYONIC BONE-FORMATION DURING POSTNATAL-GROWTH AND IN FRACTURE REPAIR

A number of proteins have recently been identified which play roles in regulating bone development. One important example is Indian hedgehog (Ihh) which is secreted by the prehyprtrophic chondrocytes. Ihh acts as an activator of a second secreted factor, parathyroid hormone-relat ed protein (PTHrP), which, in turn, negatively regulates the rate of c hondrocyte differentiation. Here we examine the expression of these ge nes and their molecular targets during different stages of bone develo pment. In addition to regulating PTHrP expression in the perichondrium , we find evidence that Ihh may also act on the chondrocytes themselve s at particular stages. As bone growth continues postnatally in mammal s and the developmental process is reactivated during fracture repair, understanding the molecular basis regulating bone development is of m edical relevance. We find that the same molecules that regulate embryo nic endochondral ossification are also expressed during postnatal bone growth and fracture healing, suggesting that these processes are cont rolled by similar mechanisms. (C) 1998 Elsevier Science Ireland Ltd.