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Adipose-derived mesenchymal stem cells (ADMSCs), a population of self-renewing multipotent cells, are a well-recognized source of potential bone precursors with significant clinical potential for tissue regeneration. We previously showed that overexpressing stearoyl-CoA desaturase 1 (SCD-1) promotes osteogenic differentiation of mesenchymal stem cells. Micro-RNAs (miRNAs) are noncoding RNAs recently recognized to play key roles in many developmental processes, and miRNA let-7c is downregulated during osteoinduction. We found that let-7c was upregulated in the serum of patients with postmenopausal osteoporosis compared with healthy controls. Levels of let-7c during osteogenic differentiation of ADMSCs were examined under oxidative stress in vitro and found to be upregulated. Overexpression of let-7c inhibited osteogenic differentiation, whereas inhibition of let-7c function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase activity, and matrix mineralization. The luciferase reporter assay was used to validate SCD-1 as a target of let-7c. Further experiments showed that silencing of SCD-1 significantly attenuated the effect of let-7c inhibitor on osteoblast markers, providing strong evidence that let-7c modulates osteogenic differentiation by targeting SCD-1. Inhibition of let-7c promoted the translocation of \u03b2-catenin into nuclei, thus activating Wnt\/\u03b2-catenin signaling. Collectively, these data suggest that let-7c is induced under oxidative stress conditions and in osteoporosis, reducing SCD-1 protein levels, switching off Wnt\/\u03b2-catenin signaling, and inhibiting osteogenic differentiation. Thus, let-7c may be a potential therapeutic target in the treatment of osteoporosis and especially postmenopausal osteoporosis. <\/jats:p>","DOI":"10.1152\/ajpcell.00211.2018","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T19:49:12Z","timestamp":1541015352000},"page":"C57-C69","source":"Crossref","is-referenced-by-count":40,"title":["Let-7c regulates proliferation and osteodifferentiation of human adipose-derived mesenchymal stem cells under oxidative stress by targeting SCD-1"],"prefix":"10.1152","volume":"316","author":[{"given":"Zihui","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanshan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 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