Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

Neha S. Dole, Courtney M. Mazur, Claire Acevedo, Justin P. Lopez, David A. Monteiro, Tristan W. Fowler, Bernd Gludovatz, Flynn Walsh, Jenna N. Regan, Sara Messina, Daniel S. Evans, Thomas F. Lang, Bin Zhang, Robert O. Ritchie, Khalid S. Mohammad, Tamara Alliston

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Resistance to fracture requires healthy bone mass and quality. However, the cellular mechanisms regulating bone quality are unclear. Dole et al. show that osteocyte-intrinsic TGF-β signaling maintains bone quality through perilacunar/canalicular remodeling. Thus, osteocytes mediate perilacunar/canalicular remodeling and osteoclast-directed remodeling to cooperatively maintain bone quality and mass and prevent fragility.

Original languageEnglish (US)
Pages (from-to)2585-2596
Number of pages12
JournalCell Reports
Volume21
Issue number9
DOIs
StatePublished - Nov 28 2017

Keywords

  • TGF-β
  • bone fragility
  • bone quality
  • osteocyte
  • perilacunar/canalicular remodeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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