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Previous studies have demonstrated that miR-146a affects osteoblast (OB) and osteoclast (OC) formation. However, these findings have yet to be identified in vivo, and it is unclear whether miR-146a is related to postmenopausal osteoporosis. Here, we demonstrated that miR-146a knockout protects bone loss in mouse model of estrogen-deficient osteoporosis, and miR-146a inhibits OB and OC activities in vitro and in vivo. MiR-146a\u2212\/\u2212 mice displayed the same bone mass as the wild type (WT) but exhibited a stronger bone turnover than the WT did under normal conditions. Nevertheless, miR-146a\u2212\/\u2212 mice showed an increase in bone mass after undergoing ovariectomy (OVX) compared with those subjected to sham operation. OC activities were impaired in the miR-146a\u2212\/\u2212 mice exposed to estrogen deficiency, which was diametrically opposite to the enhanced bone resorption ability of WT. Macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-\u03baB ligand (RANKL)\/osteoprotegerin (OPG) from a bone microenvironment affect this extraordinary phenomenon. Therefore, our results implicate that miR-146a plays a key role in estrogen deficiency\u2013induced osteoporosis, and the inhibition of this molecule provides skeleton protection. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.3832","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T18:29:42Z","timestamp":1564424982000},"page":"2149-2161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["MiR-146a Deletion Protects From Bone Loss in OVX Mice by Suppressing RANKL\/OPG and M-CSF in Bone Microenvironment"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5744-3097","authenticated-orcid":false,"given":"Jingyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences (SIBS) Chinese Academy of Sciences (CAS) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Xu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences (SIBS) Chinese Academy of Sciences (CAS) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoli","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penglei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"2024021014461117600_jbmr3832-bib-0001","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet."},{"key":"2024021014461117600_jbmr3832-bib-0002","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMcp1513724","article-title":"Clinical practice. 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