Don't hedge your bets: hedgehog signaling as a central mediator of endochondral bone development and cartilage diseases.

Published

Journal Article

Cell differentiation and patterning are vital processes in the development of the appendicular skeleton. The hedgehog (Hh) signaling pathway plays a central role in regulating the anterior-posterior axis of the distal limb as well as the length of endochondral bones. Ligand-induced Hh signaling inhibits the processing of the Gli transcription factors from activator to repressor isoforms. In the growth plate, Indian hedgehog inhibits Gli processing, resulting in accumulation of Gli activators that induce chondrocyte maturation and hypertrophic differentiation. Parathyroid hormone-like hormone promote and Gli processing to repressor forms, thus regulating the rate of hypertrophic differentiation. In cartilage diseases such as osteoarthritis and cartilage tumors, there is a recapitulation of developmental processes that involve increased Hh signaling. Studies have shown that pharmacological inhibitors of Hh signaling can attenuate the progression osteoarthritis and cartilage tumor growth. Thus, Hh blockade can serve as a potential therapy for the treatment of various cartilage diseases.

Full Text

Duke Authors

Cited Authors

  • Rockel, JS; Alman, BA

Published Date

  • June 2011

Published In

Volume / Issue

  • 29 / 6

Start / End Page

  • 810 - 815

PubMed ID

  • 21308758

Pubmed Central ID

  • 21308758

Electronic International Standard Serial Number (EISSN)

  • 1554-527X

International Standard Serial Number (ISSN)

  • 0736-0266

Digital Object Identifier (DOI)

  • 10.1002/jor.21372

Language

  • eng