{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T01:10:21Z","timestamp":1773018621890,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370894"],"award-info":[{"award-number":["82370894"]}],"id":[{"id":"10.13039\/501100001809","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":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The Wnt\/\u03b2\u2010catenin pathway and its bone\u2010specific inhibitor, sclerostin, play important roles in skeletal development and homeostasis. The humanized sclerostin antibody, romosozumab, can significantly increase bone mineral density (BMD) of patients with osteoporosis, but it may also increase cardiovascular adverse events, particularly in male patients. We try to investigate the effects of novel aptamers targeting the sclerostin loop3 on the skeleton and muscle of orchiectomized (ORX) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After 12\u2009weeks of ORX surgery, mice were randomly assigned to receive treatment with sclerostin aptamers (Apc001OA or Apc001OA\u2010d6), alendronate (ALN), teriparatide (PTH 1\u201334) or phosphate\u2010buffered saline (PBS). After 12\u2009weeks of treatment, skeletal and muscle properties and safety indicators were evaluated in detail.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with Apc001OA and Apc001OA\u2010d6 significantly increased trabecular BMD at the femur by +11.9% and +17.1%, improved parameters of bone microarchitecture (BV\/TV by +84.5% and +106.8%), bone strength (maximum load by +30.5% and +31.6%) and bone histological properties (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. PBS group). The therapeutic effects were similar among Apc001OA, Apc001OA\u2010d6, ALN and PTH 1\u201334 groups (all <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). After treatment with Apc001OA or Apc001OA\u2010d6, serum sclerostin levels significantly decreased by 25.0% and 24.9% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. PBS group). The expression levels of key genes in the Wnt\/\u03b2\u2010catenin pathway, Ctnnb1 and Lef1 significantly increased by 2.4\u2010 and 3.4\u2010fold in the Apc001OA group and by 2.5\u2010 and 3.5\u2010fold in the Apc001OA\u2010d6 group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. PBS group), indicating that the aptamers improved bone properties through activating Wnt\/\u03b2\u2010catenin pathway. Apc001OA and Apc001OA\u2010d6 significantly improved rotarod latency (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. PBS group) of ORX mice, and Apc001OA\u2010d6 could increase forelimb grip strength. Apc001OA, Apc001OA\u2010d6 and PTH 1\u201334 improved histological properties of muscle in ORX mice. No lesions or pathological changes were observed in the heart, aortic roots, liver, spleen, lungs or kidneys. Immunohistochemistry revealed no abnormal staining of interleukin 6 (IL\u20106) and tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) in the heart. There was no significant difference in serum concentrations of cardiac functional biomarkers, including creatine kinase\u2010MB (CK\u2010MB), cardiac troponin I (cTnI), B\u2010type natriuretic peptide (BNP) and inflammatory mediators (IL\u20106 and TNF\u2010\u03b1) across all groups, indicating that Apc001OA and Apc001OA\u2010d6 had no adverse cardiovascular effects in ORX mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The novel aptamers Apc001OA and Apc001OA\u2010d6, targeting sclerostin loop3, could significantly increase BMD and improve bone microarchitecture, bone biomechanics, muscle function and histological properties of muscle and bone in ORX mice, without adverse cardiovascular effects. These aptamers may serve as potential agents for treating osteoporosis and sarcopenia in men.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13831","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T04:13:26Z","timestamp":1749442406000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel Aptamers Targeting Sclerostin Loop3 Improve Skeletal and Muscle Properties Without Adverse Cardiovascular Effects in Orchiectomized Mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Bingna","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine Hong Kong Baptist University  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanye","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibo","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine Hong Kong Baptist University  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine Hong Kong Baptist University  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-4902","authenticated-orcid":false,"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC201708010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00012-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4821"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.17800"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-022-06523-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607948"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-023-01477-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081660"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1287972"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155638"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2024.105385"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjae026"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4235\/agmr.22.0036"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.168351"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202003563"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31997-8"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.63177"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2023.102073"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2020.1782592"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2024.102146"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80365"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.12.035"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1996848"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1805"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.01.012"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11030806"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305224"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708322"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02163"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-023-00238-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158320"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094895"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2023.09.007"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28946"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnaa016"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.afos.2020.02.003"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8540-5"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13831","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:22:47Z","timestamp":1754914967000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jcsm.13831"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13831","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13831"}}