{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:54:07Z","timestamp":1792526047513,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T00:00:00Z","timestamp":1647734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102017R1E1A1A01075126"],"award-info":[{"award-number":["NRF\u20102017R1E1A1A01075126"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102021R1A5A8029876"],"award-info":[{"award-number":["NRF\u20102021R1A5A8029876"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102019M3E5D1A02068575"],"award-info":[{"award-number":["NRF\u20102019M3E5D1A02068575"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mitochondrial oxidative phosphorylation (OxPhos) is a critical regulator of skeletal muscle mass and function. Although muscle atrophy due to mitochondrial dysfunction is closely associated with bone loss, the biological characteristics of the relationship between muscle and bone remain obscure. We showed that muscle atrophy caused by skeletal muscle\u2010specific CR6\u2010interacting factor 1 knockout (MKO) modulates the bone marrow (BM) inflammatory response, leading to low bone mass.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MKO mice with lower muscle OxPhos were fed a normal chow or high\u2010fat diet and then evaluated for muscle mass and function, and bone mineral density. Immunophenotyping of BM immune cells was also performed. BM transcriptomic analysis was used to identify key factors regulating bone mass in MKO mice. To determine the effects of BM\u2010derived CXCL12 (C\u2013X\u2013C motif chemokine ligand 12) on regulation of bone homeostasis, a variety of BM niche\u2010resident cells were treated with recombinant CXCL12. Vastus lateralis muscle and BM immune cell samples from 14 patients with hip fracture were investigated to examine the association between muscle function and BM inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MKO mice exhibited significant reductions in both muscle mass and expression of OxPhos subunits but increased transcription of mitochondrial stress response\u2010related genes in the extensor digitorum longus (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). MKO mice showed a decline in grip strength and a higher drop rate in the wire hanging test (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Micro\u2010computed tomography and von Kossa staining revealed that MKO mice developed a low mass phenotype in cortical and trabecular bone (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Transcriptomic analysis of the BM revealed that mitochondrial stress responses in skeletal muscles induce an inflammatory response and adipogenesis in the BM and that the CXCL12\u2013CXCR4 (C\u2013X\u2013C chemokine receptor 4) axis is important for T\u2010cell homing to the BM. Antagonism of CXCR4 attenuated BM inflammation and increased bone mass in MKO mice. In humans, patients with low body mass index (BMI\u00a0=\u00a017.2\u00a0\u00b1\u00a00.42\u00a0kg\/m<jats:sup>2<\/jats:sup>) harboured a larger population of proinflammatory and cytotoxic senescent T\u2010cells in the BMI (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and showed reduced expression of OxPhos subunits in the vastus lateralis, compared with controls with a normal BMI (23.7\u00a0\u00b1\u00a00.88\u00a0kg\/m<jats:sup>2<\/jats:sup>) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Defects in muscle mitochondrial OxPhos promote BM inflammation in mice, leading to decreased bone mass. Muscle mitochondrial dysfunction is linked to BM inflammatory cytokine secretion via the CXCL12\u2013CXCR4 signalling axis, which is critical for inducing low bone mass.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12975","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T15:39:32Z","timestamp":1647790772000},"page":"1785-1799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Skeletal muscle mitoribosomal defects are linked to low bone mass caused by bone marrow inflammation in male mice"],"prefix":"10.1002","volume":"13","author":[{"given":"Jingwen","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Medical Science Chungnam National University  Daejeon Korea"},{"name":"Laboratory of Endocrinology and Immune System Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Kyun","family":"Chung","sequence":"additional","affiliation":[{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Sun","family":"Moon","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Immune System Chungnam National University School of Medicine  Daejeon Korea"},{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Thi","family":"Nga","sequence":"additional","affiliation":[{"name":"Department of Medical Science Chungnam National University  Daejeon Korea"},{"name":"Laboratory of Endocrinology and Immune System Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Yeop","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Science Chungnam National University  Daejeon Korea"},{"name":"Laboratory of Endocrinology and Immune System Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Science Chungnam National University  Daejeon Korea"},{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Young","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Science Chungnam National University  Daejeon Korea"},{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul Gi","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medical Science Chungnam National University  Daejeon Korea"},{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongryeol","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon Korea"},{"name":"Samsung Biomedical Research Institute Samsung Medical Center  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangguo","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine Kyungpook National University  Daegu Korea"},{"name":"Department of Internal Medicine, Rheumatology and Immunology The Affiliated Hospital of Yanbian University  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je\u2010Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine Kyungpook National University  Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Tsukasaki","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Sasako","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Metabolic Diseases, Graduate School of Medicine The University of Tokyo  Tokyo 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