Hedgehog signaling underlying tendon and enthesis development and pathology

Fei Fang, McKenzie Sup, Andrew Luzzi, Xavier Ferrer, Stavros Thomopoulos

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


Hedgehog (Hh) signaling has been widely acknowledged to play essential roles in many developmental processes, including endochondral ossification and growth plate maintenance. Furthermore, a rising number of studies have shown that Hh signaling is necessary for tendon enthesis development. Specifically, the well-tuned regulation of Hh signaling during development drives the formation of a mineral gradient across the tendon enthesis fibrocartilage. However, aberrant Hh signaling can also lead to pathologic heterotopic ossification in tendon or osteophyte formation at the enthesis. Therefore, the therapeutic potential of Hh signaling modulation for treating tendon and enthesis diseases remains uncertain. For example, increased Hh signaling may enhance tendon-to-bone healing by promoting the formation of mineralized fibrocartilage at the healing interface, but pathologic heterotopic ossification may also be triggered in the adjacent tendon. Further work is needed to elucidate the distinct functions of Hh signaling in the tendon and enthesis to support the development of therapies that target the pathway.

Original languageEnglish
Pages (from-to)87-103
Number of pages17
JournalMatrix Biology
StatePublished - Jan 2022
Externally publishedYes


  • Development
  • Fibrocartilage
  • Growth plate
  • Healing
  • Hedgehog signaling
  • Heterotopic ossification
  • Mineralization
  • Tendon enthesis


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