{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:30:55Z","timestamp":1788633055476,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heilongjiang Provincial Traditional Chinese Medicine Research Project","award":["ZHY2025-135"],"award-info":[{"award-number":["ZHY2025-135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Osteoporosis (OP) is a metabolic bone disease characterized by reduced bone mass and impaired bone microarchitecture, significantly impacting patients\u2019 quality of life. Stigmasterol (STG), a natural plant sterol, has been reported to possess multiple biological activities. However, its effects on OP bone formation and underlying molecular mechanisms remain unclear. The effects of STG on OP bone formation and potential mechanisms were investigated through in vivo and in vitro experiments combined with network pharmacology analysis. An OP model was established in ovariectomized (OVX) rats, and the bone-protective effects of STG were evaluated via micro-CT analysis and histological staining. In vitro experiments, MC3T3-E1 pre-osteoblasts were used to assess STG\u2019s influence on osteogenic differentiation through Western blot analysis and ALP\/ARS staining. Network pharmacology methods were used to predict potential targets and signaling pathways for STG in OP treatment, followed by mechanism validation. STG significantly improved bone microarchitecture in OVX rats, increased key osteogenic marker expression, and promoted MC3T3-E1 osteogenic differentiation in a dose-dependent manner. Network pharmacology analysis predicted 278 potential targets for STG in treating OP, with pathway enrichment analysis indicating significant involvement of the JAK\/STAT pathway. Mechanistic studies revealed that STG promotes osteogenic differentiation by activating the JAK2\/STAT3 signaling cascade. As an osteogenic promoter, STG effectively alleviates bone loss and enhances osteoblast differentiation by activating the JAK2\/STAT3 signaling pathway.<\/jats:p>","DOI":"10.3390\/cimb48030337","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:59:36Z","timestamp":1774267176000},"page":"337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Mechanism of Action of Stigmasterol in Bone Formation in Osteoporosis"],"prefix":"10.3390","volume":"48","author":[{"given":"Cailian","family":"Lu","sequence":"first","affiliation":[{"name":"Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi 154000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi 154000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbo","family":"Liu","sequence":"additional","affiliation":[{"name":"The Cell Biology Laboratory, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirui","family":"L\u00fc","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi 154000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi 154000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67631","DOI":"10.12775\/QS.2026.50.67631","article-title":"Postmenopausal Osteoporosis: From Mechanisms to Modern Therapies","volume":"50","author":"Lambach","year":"2026","journal-title":"Qual. 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