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

Journal Article · · Cell Reports
 [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)
+ Show Author Affiliations

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1410487
Alternate ID(s):
OSTI ID: 1420129
Journal Information:
Cell Reports, Vol. 21, Issue 9; ISSN 2211-1247
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 86 works
Citation information provided by
Web of Science

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Cited By (18)

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Deciphering the Relevance of Bone ECM Signaling journal December 2020
Different effects of soybean isoflavone genistein on transforming growth factor levels during orthodontic tooth movement among young and old rabbits journal January 2019
Different effects of soybean isoflavone genistein on transforming growth factor levels during orthodontic tooth movement among young and old rabbits journal January 2019
Phenotype and Viability of MLO-Y4 Cells Is Maintained by TGFβ3 in a Serum-Dependent Manner within a 3D-Co-Culture with MG-63 Cells journal June 2018
Deficiency of stress‐associated gene Nupr1 increases bone volume by attenuating differentiation of osteoclasts and enhancing differentiation of osteoblasts journal May 2019
Glucocorticoids cause mandibular bone fragility and suppress osteocyte perilacunar-canalicular remodeling journal December 2018
The lack of neuropeptide Y‐Y 1 receptor signaling modulates the chemical and mechanical properties of bone matrix journal January 2020
Effect of GARP on osteogenic differentiation of bone marrow mesenchymal stem cells via the regulation of TGFβ1 in vitro journal January 2019
Dual Function of Magnesium in Bone Biomineralization journal October 2019
Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis journal November 2019
Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors journal March 2020
Effect of GARP on osteogenic differentiation of bone marrow mesenchymal stem cells via the regulation of TGFβ1 in vitro journal January 2019
TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis journal June 2019
A Review of the Impact of Implant Biomaterials on Osteocytes journal April 2018
Investigating Osteocytic Perilacunar/Canalicular Remodeling journal June 2019
YAP and TAZ Mediate Osteocyte Perilacunar/Canalicular Remodeling journal September 2019
Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis journal November 2019

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60 APPLIED LIFE SCIENCES
osteocyte
TGF-β
bone quality
perilacunar/canalicular remodeling
bone fragility