Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development

Vertebrate skeletogenesis requires a well-coordinated transition from chond rogenesis to osteogenesis. Hypertrophic chondrocytes in the growth plate pl ay a pivotal role in this transition. Parathyroid hormone-related peptide ( PTHrP), synthesized in the periarticular growth plate, regulates the site a t which hypertrophy occurs. By comparing PTH/PTHrP recepfor(-/-)/wild-type (PPR-/-/wild-type) chimeric mice with Ihh(-/-);PPR-/-/wild-type chimeric an d Ihh(-/-)/wild-type chimeric mice, we provide in vivo evidence that Indian hedgehog(Ihh), synthesized by prehypertrophic and hypertrophic chondrocyte s, regulates the site of hypertrophic differentiation by signaling to the p eriarticular growth plate and also determines the site of hone collar forma tion in the adjacent perichondrium. By providing crucial local signals from prehypertrophic and hypertrophic chondrocytes to both chondrocytes and pre osteoblasts, Ihh couples chondrogenesis to osteogenesis in endochondral bon e development.