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Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Osteoporosis (OP) is a chronic, systemic skeletal disorder characterized by progressive bone loss and microarchitectural deterioration, which increases fracture susceptibility and presents a challenging set of global healthcare problems. Current pharmacological interventions are limited by adverse effects, high costs, and insufficient long-term efficacy. Here, we identify snow crab shell-derived polypeptides (SCSP) as a potent osteoprotective agent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SCSP were extracted and characterized. Using an ovariectomized (OVX) mouse osteoporosis model, mice received daily oral SCSP (50, 100 mg\/kg) or saline for 8 weeks. Bone microstructure (micro-CT), histomorphometry (H&amp;amp;E, Masson, TRAP), immunohistochemistry, and serum bone turnover markers were analyzed. In vitro, SCSP (100, 200 \u03bcg\/ml) effects on osteogenic\/adipogenic differentiation in MSCs\/preosteoblasts were assessed via staining (ARS, ALP, Oil Red O) and molecular analyses (Western blot, qPCR, RNA-Seq).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SCSP, enriched in glutamic acid, aspartic acid, and lysine, significantly enhances bone mineral density, restores trabecular architecture, and preserves bone tissue integrity in an ovariectomy-induced OP mouse model without detectable systemic toxicity. At the molecular level, SCSP treatment induces the expression cell cycle regulators and motor protein pathways in osteoblasts while suppressing pro-inflammatory signaling networks, thereby re-establishing osteoblast-osteoclast balance and restoring calcium and phosphorus homeostasis. This combined mechanism promotes osteogenesis while simultaneously suppressing adipogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings position SCSP as a promising natural therapeutic for OP and provide key mechanistic insights that may guide future bone-targeted interventions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1605422","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:25:27Z","timestamp":1756099527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Crab shell polypeptides enhance calcium dynamics and osteogenic activity in osteoporosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaolei","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmeng","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiane","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daijie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1038\/s41598-018-20835-x","article-title":"CPAP3 proteins in the mineralized cuticle of a decapod crustacean","volume":"8","author":"Abehsera","year":"2018","journal-title":"Sci. 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