{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:16:07Z","timestamp":1751516167900,"version":"3.41.0"},"reference-count":46,"publisher":"Canadian Science Publishing","issue":"4","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p> Although tumor necrosis factor \u03b1 (TNF-\u03b1)-mediated inflammation significantly impacts osteoporosis, the mechanisms underlying the osteogenic differentiation defects of bone marrow-derived mesenchymal stem cells (BM-MSCs) caused by TNF-\u03b1 remain poorly understood. We found that TNF-\u03b1 stimulation of murine BM-MSCs significantly upregulated the expression levels of several microRNAs (miRNAs), including let-7f-5p, but this increase was significantly reversed by treatment with the kinase inhibitor BAY 11-7082. To study gain- or loss of function, we transfected cells with an miRNA inhibitor or miRNA mimic. We then demonstrated that let-7f-5p impaired osteogenic differentiation of BM-MSCs in the absence and presence of TNF-\u03b1, as evidenced by alkaline phosphatase and alizarin red staining as well as quantitative assays of the mRNA levels of bone formation marker genes in differentiated BM-MSCs. Moreover, let-7f-5p targets the 3\u2032 untranslated region of Nucleoside diphosphate kinase 4 (Nme4) mRNA and negatively regulates Nme4 expression in mouse BM-MSCs. Ectopic expression of Nme4 completely reversed the inhibitory effects of the let-7f-5p mimic on osteogenic differentiation of mouse BM-MSCs. Furthermore, inhibition of let-7f-5p or overexpression of Nme4 in BM-MSCs restored in-vivo bone formation in an ovariectomized animal model. Collectively, our work indicates that let-7f-5p is involved in TNF-\u03b1-mediated reduction of BM-MSC osteogenesis via targeting Nme4. <\/jats:p>","DOI":"10.1139\/bcb-2020-0281","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T18:13:38Z","timestamp":1627064018000},"page":"488-498","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The let-7f-5p\u2013Nme4 pathway mediates tumor necrosis factor \u03b1-induced impairment in osteogenesis of bone marrow-derived mesenchymal stem cells"],"prefix":"10.1139","volume":"99","author":[{"given":"Ying-Jie","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China."},{"name":"Department of Orthopaedics, Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, 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