{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:43:51Z","timestamp":1787813031353,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","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>Osteosarcopenia, characterised by concurrent bone loss and muscle atrophy, presents a significant challenge in aging populations, particularly in postmenopausal women. The current therapeutic options potentially treat bone and muscle loss independently, highlighting the importance of an integrated approach. This study aimed to investigate the effects of branched\u2010chain amino acid (BCAA) supplementation on muscle and bone health using ovariectomised (OVX) mice, a model for postmenopausal osteoporosis and sarcopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female C57BL\/6 mice were divided into sham\u2010operated and OVX groups, with OVX mice further subdivided to receive 0.25\u2009mg\/kg (Low) or 1\u2009mg\/kg (High) of BCAA supplementation for 16\u2009weeks. Muscle mass, function and mitochondrial health were assessed alongside bone mineral density (BMD), bone turnover markers and histological evaluations. Additionally, the study explored mechanistic insights into sclerostin modulation and its influence on Wnt signalling through plasma and tissue analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The hind limb fat mass was increased in the OVX group but reduced with BCAA supplementation, while hindlimb lean mass (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and total lean mass (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) were significantly higher in the OVX\u2009+\u2009High\u2010BCAA group compared with the OVX group. Gastrocnemius muscle weight was lower in the OVX group but improved (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) with both Low\u2010 and High\u2010BCAA supplementation. BCAA preserved bone microarchitecture by improving cortical thickness (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and modulating bone turnover markers, including osteocalcin (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) levels. Plasma sclerostin levels were regulated, suggesting a role in bone remodelling. In muscle, BCAA enhanced hypertrophy by upregulating MHC expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and downregulating atrophy markers such as Atrogin\u20101 (Low\u2010BCAA,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; High BCAA,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and MuRF\u20101 (Low\u2010BCAA,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; High BCAA,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Additionally, BCAA mitigated the cytotoxic effects of H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      in osteocytic MLO\u2010Y4 cells, reducing sclerostin levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and improving cellular viability (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In C2C12 cells, BCAA reversed sclerostin\u2010induced muscle atrophy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), increasing MHC expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and myotube diameter (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) while reducing Atrogin\u20101 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and MuRF\u20101 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BCAA supplementation alleviates muscle atrophy and partially preserves bone microarchitecture in OVX mice. Importantly, our data highlight bone\u2010derived sclerostin as a molecular link that transmits bone signals to muscle; BCAA mitigates osteosarcopenia by modulating this bone\u2010to\u2010muscle endocrine axis via Wnt signalling. Although improvements in bone structure were modest, the findings position BCAAs as a promising adjunct therapy targeting the integrated bone\u2013muscle unit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70105","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:27:33Z","timestamp":1761762453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of Branched\u2010Chain Amino Acids in Mitigating Osteosarcopenia: An Experimental Study Using Ovariectomised Mice Models"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9056-0073","authenticated-orcid":false,"given":"Geum\u2010Hwa","family":"Lee","sequence":"first","affiliation":[{"name":"Research Institute of Clinical Medicine of Jeonbuk National University\u2010Biomedical Research Institute of Jeonbuk National University Hospital  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa\u2010Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute of Clinical Medicine of Jeonbuk National University\u2010Biomedical Research Institute of Jeonbuk National University Hospital  Jeonju Republic of Korea"},{"name":"Non\u2010Clinical Evaluation Center, Biomedical Research Institute Jeonbuk National University Hospital  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Jae","family":"Lim","sequence":"additional","affiliation":[{"name":"Research Institute of Clinical Medicine of Jeonbuk National University\u2010Biomedical Research Institute of Jeonbuk National University Hospital  Jeonju Republic of Korea"},{"name":"Non\u2010Clinical Evaluation Center, Biomedical Research Institute Jeonbuk National University Hospital  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se\u2010Woong","family":"Ko","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Institute of New Drug Development Jeonbuk National University  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Jung","family":"Chae","sequence":"additional","affiliation":[{"name":"Research Institute of Clinical Medicine of Jeonbuk National University\u2010Biomedical Research Institute of Jeonbuk National University Hospital  Jeonju Republic of Korea"},{"name":"Non\u2010Clinical Evaluation Center, Biomedical Research Institute Jeonbuk National University Hospital  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Jung","family":"Yoon","sequence":"additional","affiliation":[{"name":"Research Institute of Clinical Medicine of Jeonbuk National University\u2010Biomedical Research Institute of Jeonbuk National University Hospital  Jeonju Republic of Korea"},{"name":"Department of Orthopedic Surgery Jeonbuk National University Medical School  Jeonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.5371\/hp.2022.34.1.10"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu023"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2000.tb04694.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2011.01.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/87.5.1562S"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9758-y"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04679-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-00990-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205343"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-07605-6"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.08.016"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.2020-0356"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.08.005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.01.002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101456"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1997.12.12.2014"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85289"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12178"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.584147"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X12466608"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.02.005"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.10.008"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094895"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10004"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062295"},{"key":"e_1_2_7_27_1","first-page":"71","article-title":"Identification of Sclerostin as a Putative New Myokine Involved in the Muscle\u2010to\u2010Bone Crosstalk","volume":"9","author":"Magar\u00f2 M. S.","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080216"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03093-6"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.03.008"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11030806"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000009534"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.5371\/hp.2022.34.1.1"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70105","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70105","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:41:50Z","timestamp":1772959310000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jcsm.70105"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70105","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"2025-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70105"}}