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

Neha S Dole1, Courtney M Mazur2, Claire Acevedo3

  • 1Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.

Cell Reports
|November 30, 2017
PubMed

Insights

Transforming growth factor beta (TGF-β) controls bone quality by regulating perilacunar/canalicular remodeling (PLR) within osteocytes. This discovery highlights osteocytes as key regulators of bone homeostasis and fragility.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Bone Biology

Background:

  • Poor bone quality increases fracture risk in conditions like diabetes, aging, and osteogenesis imperfecta.
  • Mechanisms governing bone quality are poorly understood, hindering the development of diagnostic and therapeutic strategies.
  • Transforming growth factor beta (TGF-β) signaling is implicated in bone material quality, but its specific cellular target remains unidentified.

Purpose of the Study:

  • To investigate whether TGF-β signaling controls bone quality through osteocyte-mediated perilacunar/canalicular remodeling (PLR).
  • To identify the cellular mechanisms by which TGF-β influences bone quality.

Main Methods:

  • Utilized pharmacological inhibitors of TGF-β signaling.
  • Employed genetically modified mice with osteocyte-specific defects in TGF-β type II receptor (TβRIIocy-/-).
  • Assessed bone quality and perilacunar/canalicular remodeling (PLR) in experimental models.

Main Results:

  • Demonstrated that TGF-β signaling regulates perilacunar/canalicular remodeling (PLR) in an osteocyte-intrinsic manner.
  • Confirmed that TGF-β controls bone quality through osteocyte-mediated PLR.
  • Established osteocytes as the critical cellular mediators of TGF-β's effect on bone quality.

Conclusions:

  • Osteocytes are central to the biological control of bone quality via perilacunar/canalicular remodeling (PLR).
  • Osteocyte-mediated PLR is fundamental for maintaining bone homeostasis.
  • This study provides critical insights into bone fragility and potential therapeutic targets for bone quality deficits.
Keywords:
TGF-βbone fragilitybone qualityosteocyteperilacunar/canalicular remodeling

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