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

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 (TβRII ocy-/-), 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.
 [1] ;  [2] ;  [3] ;  [2] ;  [2] ;  [1] ;  [4] ;  [4] ;  [5] ;  [6] ;  [7] ;  [1] ;  [8] ;  [6] ;  [5] ;  [2]
  1. Univ. of California, San Francisco, CA (United States)
  2. Univ. of California, San Francisco, CA (United States); UC Berkeley/UCSF Graduate Program in Bioengineering, San Francisco, CA (United States)
  3. Univ. of California, San Francisco, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Indiana Univ. School of Medicine, Indianapolis, IN (United States)
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
  7. California Pacific Medical Center Research Institute, San Francisco, CA (United States)
  8. Icahn School of Medicine at Mount Sinai, New York, NY (United States)
Publication Date:
Grant/Contract Number:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 21; Journal Issue: 9; Journal ID: ISSN 2211-1247
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
60 APPLIED LIFE SCIENCES; osteocyte; TGF-β; bone quality; perilacunar/canalicular remodeling; bone fragility
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1420129