{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:30:31Z","timestamp":1785551431599,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["111\u20102320\u2010B\u2010039\u2010070\u2010MY3"],"award-info":[{"award-number":["111\u20102320\u2010B\u2010039\u2010070\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","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":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The progressive deterioration of tissue\u2013tissue crosstalk with aging causes a striking impairment of tissue homeostasis and functionality, particularly in the musculoskeletal system. Rejuvenation of the systemic and local milieu via interventions such as heterochronic parabiosis and exercise has been reported to improve musculoskeletal homeostasis in aged organisms. We have shown that Ginkgolide B (GB), a small molecule from <jats:styled-content style=\"fixed-case\"><jats:italic>Ginkgo biloba<\/jats:italic><\/jats:styled-content>, improves bone homeostasis in aged mice by restoring local and systemic communication, implying a potential for maintaining skeletal muscle homeostasis and enhancing regeneration. In this study, we investigated the therapeutic efficacy of GB on skeletal muscle regeneration in aged mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Muscle injury models were established by barium chloride induction into the hind limb of 20\u2010month\u2010old mice (aged mice) and into C2C12\u2010derived myotubes. Therapeutic efficacy of daily administrated GB (12\u00a0mg\/kg body weight) and osteocalcin (50\u00a0\u03bcg\/kg body weight) on muscle regeneration was assessed by histochemical staining, gene expression, flow cytometry, ex vivo muscle function test and rotarod test. RNA sequencing was used to explore the mechanism of GB on muscle regeneration, with subsequent in vitro and in vivo experiments validating these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GB administration in aged mice improved muscle regeneration (muscle mass, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0374; myofiber number\/field, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0001; centre nucleus, embryonic myosin heavy chain\u2010positive myofiber area, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0144), facilitated the recovery of muscle contractile properties (tetanic force, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0002; twitch force, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0005) and exercise performance (rotarod performance, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002), and reduced muscular fibrosis (collagen deposition, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and inflammation (macrophage infiltration, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). GB reversed the aging\u2010related decrease in the expression of osteocalcin (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), an osteoblast\u2010specific hormone, to promote muscle regeneration. Exogenous osteocalcin supplementation was sufficient to improve muscle regeneration (muscle mass, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0029; myofiber number\/field, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), functional recovery (tetanic force, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0059; twitch force, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.07; rotarod performance, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and fibrosis (collagen deposition, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0316) in aged mice, without an increased risk of heterotopic ossification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GB treatment restored the bone\u2010to\u2010muscle endocrine axis to reverse aging\u2010related declines in muscle regeneration and thus represents an innovative and practicable approach to managing muscle injuries. Our results revealed the critical and novel role of osteocalcin\u2013GPRC6A\u2010mediated bone\u2010to\u2010muscle communication in muscle regeneration, which provides a promising therapeutic avenue in functional muscle regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13228","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T04:06:26Z","timestamp":1681963586000},"page":"1349-1364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Ginkgolide B facilitates muscle regeneration via rejuvenating osteocalcin\u2010mediated bone\u2010to\u2010muscle modulation in aged mice"],"prefix":"10.1002","volume":"14","author":[{"given":"Belle Yu\u2010Hsuan","family":"Wang","sequence":"first","affiliation":[{"name":"Musculoskeletal Research Laboratory, SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine The Chinese University of Hong Kong  Hong Kong"},{"name":"Center for Neuromusculoskeletal Restorative Medicine CUHK InnoHK Centres, Hong Kong Science Park  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0793-8769","authenticated-orcid":false,"given":"Yi\u2010Fan","family":"Chen","sequence":"additional","affiliation":[{"name":"The Ph.D. Program for Translational Medicine, College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"},{"name":"Graduate Institute of Translational Medicine, College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"},{"name":"International Ph.D. Program for Translational Science, College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"},{"name":"Master Program in Clinical Genomics and Proteomics, School of Pharmacy Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen Wei\u2010Ting","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital The Chinese University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"The Ph.D. Program for Translational Medicine, College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6679-0020","authenticated-orcid":false,"given":"Chien\u2010Wei","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Translational Genomics &amp; Regenerative Medicine Research China Medical University Hospital, China Medical University  Taichung Taiwan"},{"name":"Department of Biomedical Engineering China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5232-5374","authenticated-orcid":false,"given":"Oscar Kuang\u2010Sheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Translational Genomics &amp; Regenerative Medicine Research China Medical University Hospital, China Medical University  Taichung Taiwan"},{"name":"Department of Orthopedics China Medical University Hospital  Taichung Taiwan"},{"name":"Institute of Clinical Medicine National Yang Ming Chiao Tung University  Taipei 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