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Integrated analyses of clinical serum samples and the GTEx database revealed a pronounced reduction in circulating FSTL1 levels in PMOP patients. In vivo, Fstl1+\/\u2212 ovariectomized mice displayed exacerbated bone loss\u2014evidenced by diminished BMD and trabecular volume\u2014together with impaired osteoblastic activity and heightened osteoclast activation. Complementary in vitro experiments showed that FSTL1 over-expression markedly enhanced osteogenic differentiation, as reflected by increased alkaline phosphatase activity and matrix mineralization, whereas FSTL1 knockdown produced the opposite effect. Conversely, FSTL1 over-expression suppressed osteoclastogenesis, while its silencing facilitated the formation of tartrate-resistant acid phosphatase-positive osteoclasts. Therapeutic administration of recombinant FSTL1 protein in vivo significantly attenuated OVX-induced bone loss and improved trabecular architecture, stimulated osteoblast differentiation, and curtailed osteoclast function. Collectively, these findings position FSTL1 as a down-regulated mediator in PMOP that modulates bone remodeling by simultaneously promoting osteogenesis and restraining osteoclastogenesis, supporting a potential association of FSTL1 with PMOP and its possible relevance as a biomarker and therapeutic target.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziag037","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:31:55Z","timestamp":1772973115000},"source":"Crossref","is-referenced-by-count":0,"title":["Follistatin-like protein 1 (FSTL1) modulates bone remodeling and attenuates bone loss in a mouse model of postmenopausal osteoporosis"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1032-6483","authenticated-orcid":false,"given":"Hao","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Rheumatology, The Second Affiliated Hospital of Soochow University , Suzhou 215004 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