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

• Published in: Cell reports (Cambridge) Vol. 21; no. 9; pp. 2585 - 2596
• Main Authors: Dole, Neha S., Mazur, Courtney M., Acevedo, Claire, Lopez, Justin P., Monteiro, David A., Fowler, Tristan W., Gludovatz, Bernd, Walsh, Flynn, Regan, Jenna N., Messina, Sara, Evans, Daniel S., Lang, Thomas F., Zhang, Bin, Ritchie, Robert O., Mohammad, Khalid S., Alliston, Tamara
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.11.2017; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; bone fragility; bone quality; osteocyte; perilacunar/canalicular remodeling; TGF-β; TGF-β; osteocyte; perilacunar/canalicular remodeling; bone quality; bone fragility
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.10.115

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. [Display omitted] •TGF-β is an osteocyte-intrinsic regulator of perilacunar/canalicular remodeling (PLR)•Osteocytes actively maintain bone quality through regulated control of PLR•Osteocytic PLR is the cellular mechanism by which TGF-β controls bone quality•Defects in PLR cause severe bone fragility, even when bone mass is normal 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.