{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:28:25Z","timestamp":1785644905960,"version":"3.56.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Osteoporosis is a common aging-related metabolic disease that mainly occurs in older adults and postmenopausal women. Despite advances in anti-osteoporosis treatment, outcomes remain unsatisfactory due to detrimental side effects. BCI hydrochloride (BCI), a selective dual-specificity phosphatase 6 (DUSP6) inhibitor, is associated with multiple cellular functions, including inhibiting tumor growth and macrophage inflammation; however, its role in regulating osteoclast differentiation remains unknown. Here, we revealed that treatment with BCI attenuated RANKL-mediated osteoclast differentiation <jats:italic>in vitro<\/jats:italic> and alleviated ovariectomy-induced osteoporosis without obvious toxicity. Specifically, BCI disrupted F-actin ring formation and bone-resorption activity and decreased osteoclast-specific gene and protein levels in a dose-dependent manner. KEGG pathway analysis, GSEA based on transcriptome sequencing, and western blot results suggested that BCI inhibited RANKL-induced osteoclastogenesis by restraining STAT3 and NF-\u03baB signaling and attenuating NF-\u03baB\/p65 interaction with NFATc1. These results revealed that BCI treatment prevented postmenopausal osteoporosis and might represent an effective approach for treating osteoporosis.<\/jats:p>","DOI":"10.3389\/fphar.2021.772540","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T04:50:07Z","timestamp":1635742207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss"],"prefix":"10.3389","volume":"12","author":[{"given":"Chenhui","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongwei","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.20892\/j.issn.2095-3941.2017.0107","article-title":"Dual-specificity Phosphatase 6 (DUSP6): a Review of its Molecular Characteristics and Clinical Relevance in Cancer","volume":"15","author":"Ahmad","year":"2018","journal-title":"Cancer Biol. 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