Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein

• DOI: 10.1126/science.273.5275.613
• Publication Date: 2006-10-27T18:30:41Z
• Authors: Andrea Vortkamp; Kaechoong Lee; Beate Lanske; Gino V. Segre; Henry M. Kronenberg; Clifford J. Tabin
• Keywords: Indian hedgehog; Parathyroid hormone-related protein; Cyclopamine; Perichondrium; Patched

Proper regulation of chondrocyte differentiation is necessary for the morphogenesis skeletal elements, yet little known about molecular this process. A chicken homolog Indian hedgehog (Ihh), a member conserved Hedgehog family secreted proteins that expressed during bone formation, has now been isolated. Ihh biological properties similar to those Sonic (Shh), including ability regulate targets Patched (Ptc) and Gli. in prehypertrophic chondrocytes cartilage where it regulates rate hypertrophic differentiation. Misexpression prevents proliferating from initiating The direct target signaling perichondrium, Gli Ptc flank expression domain Ihh. induces second signal, parathyroid hormone-related protein (PTHrP), periarticular perichondrium. Analysis PTHrP (−/−) mutant mice indicated signals its receptor chondrocytes, thereby blocking In vitro application or normal limb explants demonstrated mediates effects through formation negative feedback loop modulates