ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
Deletion of connexin43 in osteoblasts/osteocytes leads to impaired muscle formation in mice.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 96 citations in OpenAlex.
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- Correlation study between bone metabolic markers, bone mineral density, and sarcopenia.Journal of endocrinological investigation · 2024Article
- Causal relationship between sarcopenia and osteoarthritis: a bi-directional two-sample mendelian randomized study.European journal of medical research · 2023Article
- Connexin 43 hemichannels and prostaglandin EFrontiers in cell and developmental biology · 2023Review
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- Connexin 43 Channels in Osteocytes Are Necessary for Bone Mass and Skeletal Muscle Function in Aged Male Mice.International journal of molecular sciences · 2022Article
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- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
- Sarcopenia and bone health: new acquisitions for a firm liaison.Therapeutic advances in musculoskeletal disease · 2022Review
- Exploring the Temporal Correlation of Sarcopenia with Bone Mineral Density and the Effects of Osteoblast-Derived Exosomes on Myoblasts through an Oxidative Stress-Related Gene.Oxidative medicine and cellular longevity · 2022Article
- Metabolomics Coupled with Pathway Analysis Provides Insights into Sarco-Osteoporosis Metabolic Alterations and Estrogen Therapeutic Effects in Mice.Biomolecules · 2021Article
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Abstract
It is well-established that muscle forces are necessary for bone development as well as proper bone modeling and remodeling. Recent work has also suggested that bone acts as an endocrine organ that can influence the development of other organs. Connexin43 (Cx43), a gap junction protein that transduces mechanical signals, is an important determinant of cortical bone modeling. Using an osteoblast/osteocyte-specific ablation of the Cx43 gene (Gja1) driven by the 2.3-kb Col1 α1 promoter (cKO) in the mouse, in this study we confirmed reduced cortical bone thickness and density with expanded bone marrow cavity in the cKO humerus. Surprisingly, Gja1 deletion in bone cells also affected skeletal muscle development, resulting in lower fast muscle weight, grip strength, and maximum absolute and specific tetanic forces (60% to 80%, 85%, and 50%, respectively, of WT mice). The normally fast twitch extensor digitorum longus (EDL) muscle exhibited increased slow twitch fibers in cKO mice. These muscle defects were accompanied by a 40% to 60% reduction in mRNA abundance for genes encoding osteocalcin in the humerus, relative to WT mice. Accordingly, both carboxylated and undercarboxylated isoforms of osteocalcin were reduced by over 30% in the circulation of cKO mice. Moreover, the active, undercarboxylated isoform of osteocalcin (glu-OC) promoted myotube formation in C2C12 myoblast cultures, and glu-OC injections to cKO mice rescued EDL muscle cross-sectional area and grip strength in vivo. These findings demonstrate that Cx43 in osteoblasts/osteocytes indirectly modulates skeletal muscle growth and function, potentially via an endocrine effect of glu-OC.
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