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Here, we identify microRNA\u2010146a (miR\u2010146a) as an essential epigenetic switch controlling bone loss with age. Mice deficient in miR\u2010146a show regular development of their skeleton. However, while WT mice start to lose bone with age, animals deficient in miR\u2010146a continue to accrue bone throughout their life span. Increased bone mass is due to increased generation and activity of osteoblasts in miR\u2010146a\u2010deficient mice as a result of sustained activation of bone anabolic Wnt signaling during aging. Deregulation of the miR\u2010146a target genes Wnt1 and Wnt5a parallels bone accrual and osteoblast generation, which is accompanied by reduced development of bone marrow adiposity. Furthermore, miR\u2010146a\u2010deficient mice are protected from ovariectomy\u2010induced bone loss. In humans, the levels of miR\u2010146a are increased in patients suffering fragility fractures in comparison with those who do not. These data identify miR\u2010146a as a crucial epigenetic temporal regulator which essentially controls bone homeostasis during aging by regulating bone anabolic Wnt signaling. Therefore, miR\u2010146a might be a powerful therapeutic target to prevent age\u2010related bone dysfunctions such as the development of bone marrow adiposity and osteoporosis.<\/jats:p>","DOI":"10.1111\/acel.13244","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T06:17:21Z","timestamp":1603261041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["microRNA\u2010146a controls age\u2010related bone loss"],"prefix":"10.1111","volume":"19","author":[{"given":"Victoria","family":"Saferding","sequence":"first","affiliation":[{"name":"Department of Rheumatology Medical University of Vienna  Vienna Austria"},{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and 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