{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:27:13Z","timestamp":1792016833869,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3605705"],"award-info":[{"award-number":["2023YFC3605705"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YG2024ZD09"],"award-info":[{"award-number":["YG2024ZD09"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571807"],"award-info":[{"award-number":["82571807"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20ZR1435100"],"award-info":[{"award-number":["20ZR1435100"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2020YJZX0122"],"award-info":[{"award-number":["2020YJZX0122"]}],"id":[{"id":"10.13039\/100017950","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":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous research has shown that the conditional knockout of Slo1 in muscle leads to a reduction in muscle strength and inhibits myogenic differentiation. Exosomes are emerging as necessary mediators of the crosstalk between muscle and bones. The present study focused on the communication between muscle and bone to investigate the effects and mechanisms of skeletal muscle\u2010specific knockout of Slo1 on bone mass and bone metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Myf5\u2010Cre mice were mated with Slo1\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      mice to construct skeletal muscle\u2010specific Slo1 knockout mice (CKO mice). The legs of the Slo1 CKO mice were isolated, and a series of examinations were conducted to monitor bone mineral density (BMD) and bone microstructure. Exosomes were extracted from C2C12\u2010shNC and C2C12\u2010shSlo1 cells and subjected to transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting (WB). The osteogenic effect of EXO\u2010shSlo1 was examined in\u00a0vitro and in\u00a0vivo by Alkaline phosphatase (ALP) staining, q\u2010PCR, WB and microCT. RNA sequencing (RNA\u2010seq) analysis of EXO\u2010shNC and EXO\u2010shSlo1 was used to identify differentially expressed microRNAs. Mimics and inhibitors of miR\u2010222\u20103p were transfected into MC3T3\u2010E1 cells to induce differentiation. The predicted targets of miR\u2010222\u20103p were examined with Luciferase, qPCR, and WB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In Slo1 CKO mice, the bone mass decreased, and the microstructure was disrupted. TEM, NTA and WB assays showed that Slo1\u2010silenced C2C12 cells secreted exosomes and localized to MC3T3\u2010E1 cells and bone tissue through the circulation. EXO\u2010shSlo1 inhibited osteogenesis both in\u00a0vivo and in\u00a0vitro, as demonstrated by the decreased ALP activity (~40%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), osteogenic marker expression (~30%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), mineral deposition in osteoblasts and BMD. qPCR was performed to confirm the exosome RNA\u2010seq results, which indicated that miR\u2010222\u20103p was increased by three times in the EXO\u2010shSlo1 group compared with the EXO\u2010shNC group. Transfection of mimics or inhibitors of miR\u2010222\u20103p in MC3T3\u2010E1 cells inhibited or improved osteogenic differentiation. Luciferase reporter assays revealed that miR\u2010222\u20103p targets STAT3. The mRNA and protein level of STAT3 was affected by miR\u2010222\u20103p. Through inhibiting miR\u2010222\u20103p or upregulating STAT3, the EXO\u2010shSlo1\u2010mediated osteogenic inhibition of MC3T3\u2010E1 cells was ameliorated, as indicated by increased ALP activity and osteogenic marker expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Slo1 deficiency in muscle results in decreased bone mass mediated by exosomal miR\u2010222\u20103p. MiR\u2010222\u20103p binds and inhibits the transcription of STAT3 to suppress the differentiation of osteoblasts. Slo1\u2010silenced myoblasts\u2010derived exosomal miR\u2010222\u20103p inhibit osteogenesis and cause bone loss through the miR\u2010222\u20103p\/STAT3 pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70115","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T01:32:33Z","timestamp":1765243953000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Slo1 Deficient Myoblast Exosomes\u2010Derived miR\u2010222\u20103p Inhibits Osteogenic Differentiation via Targeting of STAT3"],"prefix":"10.1002","volume":"16","author":[{"given":"Yonghui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Xinhua Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Shanghai General Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Shanghai General Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Xinhua Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junran","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Xinhua Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Xinhua Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rang","family":"Xu","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Xinhua Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Xinhua Hospital Shanghai JiaoTong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa755"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12567"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155638"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2018.33.e27"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41999-020-00355-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.26242"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278279"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2006.163.9.1622"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-4-51"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303203"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.272"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081270"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1972-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.07.027"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13253"},{"key":"e_1_2_8_17_1","first-page":"175","article-title":"Wolff's Law and Bone's Structural Adaptations to Mechanical Usage: An Overview for Clinicians","volume":"64","author":"Frost H. 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