دورية أكاديمية
L‐BAIBA Synergizes with Sub‐Optimal Mechanical Loading to Promote New Bone Formation
| العنوان: | L‐BAIBA Synergizes with Sub‐Optimal Mechanical Loading to Promote New Bone Formation |
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| المؤلفون: | Matt Prideaux, Alberto Smargiassi, Gang Peng, Marco Brotto, Alexander G Robling, Lynda F Bonewald |
| المصدر: | JBMR Plus, Vol 7, Iss 6, Pp n/a-n/a (2023) |
| بيانات النشر: | Oxford University Press, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Orthopedic surgery LCC:Diseases of the musculoskeletal system |
| مصطلحات موضوعية: | ANALYSIS/QUANTITATION OF BONE, BONE HISTOMORPHOMETRY, BONE‐MUSCLE INTERACTIONS, CELLS OF BONE, OSTEOCYTES, SYSTEMS BIOLOGY‐BONE INTERACTORS, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935 |
| الوصف: | ABSTRACT The L‐enantiomer of β‐aminoisobutyric acid (BAIBA) is secreted by contracted muscle in mice, and exercise increases serum levels in humans. In mice, L‐BAIBA reduces bone loss with unloading, but whether it can have a positive effect with loading is unknown. Since synergism can be more easily observed with sub‐optimal amounts of factors/stimulation, we sought to determine whether L‐BAIBA could potentiate the effects of sub‐optimal loading to enhance bone formation. L‐BAIBA was provided in drinking water to C57Bl/6 male mice subjected to either 7 N or 8.25 N of sub‐optimal unilateral tibial loading for 2 weeks. The combination of 8.25 N and L‐BAIBA significantly increased the periosteal mineral apposition rate and bone formation rate compared to loading alone or BAIBA alone. Though L‐BAIBA alone had no effect on bone formation, grip strength was increased, suggesting a positive effect on muscle function. Gene expression analysis of the osteocyte‐enriched bone showed that the combination of L‐BAIBA and 8.25 N induced the expression of loading‐responsive genes such as Wnt1, Wnt10b, and the TGFb and BMP signaling pathways. One dramatic change was the downregulation of histone genes in response to sub‐optimal loading and/or L‐BAIBA. To determine early gene expression, the osteocyte fraction was harvested within 24 hours of loading. A dramatic effect was observed with L‐BAIBA and 8.25 N loading as genes were enriched for pathways regulating the extracellular matrix (Chad, Acan, Col9a2), ion channel activity (Scn4b, Scn7a, Cacna1i), and lipid metabolism (Plin1, Plin4, Cidec). Few changes in gene expression were observed with sub‐optimal loading or L‐BAIBA alone after 24 hours. These results suggest that these signaling pathways are responsible for the synergistic effects between L‐BAIBA and sub‐optimal loading. Showing that a small muscle factor can enhance the effects of sub‐optimal loading of bone may be of relevance for individuals unable to benefit from optimal exercise. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2473-4039 |
| العلاقة: | https://doaj.org/toc/2473-4039Test |
| DOI: | 10.1002/jbm4.10746 |
| الوصول الحر: | https://doaj.org/article/d0dfca7e0abd44d88acc13980d9fa125Test |
| رقم الانضمام: | edsdoj.0dfca7e0abd44d88acc13980d9fa125 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24734039 |
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| DOI: | 10.1002/jbm4.10746 |