High-fat and high-carbohydrate diets increase bone fragility through TGF-β-dependent control of osteocyte function.

Autor: Dole NS; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.; Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock Arkansas, USA., Betancourt-Torres A; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Kaya S; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Obata Y; Department of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA., Schurman CA; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.; UC Berkeley/UCSF Graduate Program in Bioengineering, San Francisco, California, USA., Yoon J; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Yee CS; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Khanal V; Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock Arkansas, USA., Luna CA; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Carroll M; Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock Arkansas, USA., Salinas JJ; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Miclau E; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA., Acevedo C; Department of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA.; Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA.; Department of Mechanical and Aerospace Engineering, University of California, San Diego, San Diego, California, USA., Alliston T; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.; UC Berkeley/UCSF Graduate Program in Bioengineering, San Francisco, California, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 Jul 09; Vol. 9 (16). Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1172/jci.insight.175103
Abstrakt: Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre-mediated deletion of TGF-β receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.
Databáze: MEDLINE
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