Sox9+ messenger cells orchestrate large-scale skeletal regeneration in the mammalian rib

Stephanie T. Kuwahara, Maxwell A. Serowoky, Venus Vakhshori, Nikita Tripuraneni, Neel V. Hegde, Jay R. Lieberman, J. Gage Crump, Francesca V. Mariani

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Most bones in mammals display a limited capacity for natural large-scale repair. The ribs are a notable exception, yet the source of their remarkable regenerative ability remains unknown. Here, we identify a Sox9-expressing periosteal subpopulation that orchestrates large- scale regeneration of murine rib bones. Deletion of the obligate Hedgehog co-receptor, Smoothened, in Sox9-expressing cells prior to injury results in a near-complete loss of callus formation and rib bone regeneration. In contrast to its role in development, Hedgehog signaling is dispensable for the proliferative expansion of callus cells in response to injury. Instead, Sox9- positive lineage cells require Hh signaling to stimulate neighboring cells to differentiate via an unknown signal into a skeletal cell type with dual chondrocyte/osteoblast properties. This type of callus cell may be critical for bridging large bone injuries. Thus despite contributing to only a subset of callus cells, Sox9-positive progenitors play a major role in orchestrating large-scale bone regeneration. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor’s assessment is that all the issues have been addressed (see decision letter).

Original languageEnglish (US)
Article numbere40715
StatePublished - Apr 2019
Externally publishedYes

Bibliographical note

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© Kuwahara et al.


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