{"id":367,"title":"Statins promote bone anabolism in estrogen deficiency by inducing osteogenic differentiation of skeletal stem/progenitor cells","title_zh":"他汀通过诱导骨骼干/祖细胞成骨分化促进雌激素缺乏下的骨合成","url":"https://pubmed.ncbi.nlm.nih.gov/42946859","doi":"10.1038/s43587-026-01257-1","pmid":"42946859","journal":"Nat Aging","kind":"paper","lang":"en","published_at":"2026-10-27T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Yang M","Guo J","Ye J","Meng X","Ma Y","Ni Y","Chen T","Zhang Y","Guo H","Shen G","Yuan Y","Qiao X","Wu Y","Li J","Qi X","Fang S","Wang L","Shen B"],"primary_topic":"repro-aging","topics":[{"slug":"repro-endo","score":2.0,"hits":["estradiol","menopause"]}],"topic_score":2.0,"preference_score":0.0,"preference_labels":[],"llm_score":72.0,"final_score":80.0,"score_dims":{"novelty":85,"rigor":80,"impact":65,"relevance":40,"translation":55},"recommend_reason":"机制证据较完整，提出他汀在雌激素缺乏下作用于骨骼干/祖细胞的新通路，对绝经后骨代谢和生殖内分泌管理有参考价值；但与ART、胚胎及核心生殖医学的直接相关性较弱，适合相关方向读者浏览。","keywords":["他汀","绝经后骨质疏松","骨骼干/祖细胞","LEPR+骨髓基质细胞","RAC1","成骨分化"],"selected":1,"story_id":306,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"nat-aging","journal_tier":"cns-sub","journal_if":17.0,"is_mock":false,"summary_zh":"研究探讨绝经后雌激素缺乏背景下他汀对骨代谢的作用。分析显示，绝经后女性使用他汀与骨密度年下降较慢相关；机制实验表明，阿托伐他汀在雌激素缺乏条件下特异性促进骨合成，诱导表达瘦素受体的骨髓基质细胞（含骨骼干/祖细胞）成骨分化。机制上，阿托伐他汀通过限制RAC1异戊烯化、促进NF-κB介导的Oln转录增加成骨细胞形成；雌激素则经E2-ERα通路作用于同一细胞群促进Oln转录，提示他汀以不同机制补偿雌激素信号下降。","summary":"Menopause-associated estrogen deficiency drives age-related bone loss in women. Statin use has been associated with higher bone mineral density in postmenopausal women, but whether menopause alters skeletal responses to statins remains unclear. Here, we show that statin use was associated with a slower annual decline in bone mineral density in postmenopausal women and that atorvastatin promotes bone anabolism specifically under estrogen-deficient conditions by inducing osteogenic differentiation of leptin receptor-expressing (LEPR+) bone marrow stromal cells, which include skeletal stem/progenitor cells. Atorvastatin increases osteoblast formation by restricting RAC1 prenylation and enabling nuclear factor kappa B-mediated Oln transcription. Estrogen acts on the same LEPR+ cells through estradiol-estrogen receptor-α signaling to promote Oln transcription. Thus, statins compensate for reduced estradiol-estrogen receptor-α signaling through a mechanistically distinct pathway. These findings reposition a major component of estrogen action to an earlier osteogenic stage and suggest broader implications for how statins influence stem/progenitor cell responsiveness beyond cholesterol management.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}