Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling
Year: 2017
Type: article
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 (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.
Source: Cell Reports
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Science Foundation, U.S. Department of Defense, U.S. Department of Energy, Orthopaedic Research and Education Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, Office of Science, School of Medicine, Indiana University, National Defense Science and Engineering Graduate, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, Basic Energy Sciences, Lawrence Berkeley National Laboratory
Awards: G1079818582, G1143651532, G1148965125, G1286236842, G1286251239, The mechanobiology of TGF-beta signaling in chondrocytes, G1863003419, G2141279964, The mechanistic control of bone quality and joint crosstalk by osteocytes, G2795275917, G30714459, G3083819904, Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC Supercomputer, G382641700, G419881185, G42916606, G4501827968, Graduate Research Fellowship Program (GRFP), G498139845, G5175575554, G650090426, Biomechanics of stress fracture associated with bone fragility, G6998434892, G7015462466, G7354628648, UCSF Core Center for Musculoskeletal Biology and Medicine, miRNA coordination of TGF-beta / Wnt signaling in osteocyte mechanotransduction, UCSF/UCB Joint Graduate Group in Bioengineering, G9000213115, G969889393, Mechanoregulation of Growth Factor Receptor Assembly and Signaling
OpenAlex ID: W2770060985