MicroRNA‐146a controls age‐related bone loss. Issue 11 (21st October 2020)

• Record Type: Journal Article
• Authors: Saferding, Victoria; Hofmann, Melanie; Brunner, Julia S.; Niederreiter, Birgit; Timmen, Melanie; Magilnick, Nathaniel; Hayer, Silvia; Heller, Gerwin; Steiner, Günter; Stange, Richard; Boldin, Mark; Schabbauer, Gernot; Weigl, Moritz; Hackl, Matthias; Grillari, Johannes; Smolen, Josef S.; Blüml, Stephan
• Is Part Of: Aging cell. Volume 19:Issue 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-21
• Subjects: aging -- bone metabolism -- microRNA -- osteopetrosis -- osteoporosis; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13244
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: Bone loss is one of the consequences of aging, leading to diseases such as osteoporosis and increased susceptibility to fragility fractures and therefore considerable morbidity and mortality in humans. Here, we identify microRNA‐146a (miR‐146a) as an essential epigenetic switch controlling bone loss with age. Mice deficient in miR‐146a show regular development of their skeleton. However, while WT mice start to lose bone with age, animals deficient in miR‐146a continue to accrue bone throughout their life span. Increased bone mass is due to increased generation and activity of osteoblasts in miR‐146a‐deficient mice as a result of sustained activation of bone anabolic Wnt signaling during aging. Deregulation of the miR‐146a target genes Wnt1 and Wnt5a parallels bone accrual and osteoblast generation, which is accompanied by reduced development of bone marrow adiposity. Furthermore, miR‐146a‐deficient mice are protected from ovariectomy‐induced bone loss. In humans, the levels of miR‐146a are increased in patients suffering fragility fractures in comparison with those who do not. These data identify miR‐146a as a crucial epigenetic temporal regulator which essentially controls bone homeostasis during aging by regulating bone anabolic Wnt signaling. Therefore, miR‐146a might be a powerful therapeutic target to prevent age‐related bone dysfunctions such as the development of bone marrow adiposity and osteoporosis. Abstract : We identify microRNA‐146a as a molecular clock that controls bone loss during aging by restricting bone anabolic pathways and promoting bone marrow adiposity. Loss of miR‐146a preserves bone anabolic pathways, leading to continuous increases in bone mass during aging, and protects from the development of experimental osteoporosis. Therefore, we identify miR‐146a as an essential factor regulating bone loss and suggest that targeting miR‐146a might be a powerful means to treat bone loss in diseases such as osteoporosis.