miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice

• Published in: Scientific reports Vol. 7; no. 1; p. 43191
• Main Authors: Hu, Cheng-Hu, Sui, Bing-Dong, Du, Fang-Ying, Shuai, Yi, Zheng, Chen-Xi, Zhao, Pan, Yu, Xiao-Rui, Jin, Yan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.02.2017; Nature Publishing Group
• Subjects: 13/1; 13/100; 13/89; 38; 38/77; 631/136/818; 631/337/384/331; 64/60; 692/308/2056; 692/53/2421; 692/699/2743/316/801; 82/80; 96/21; 96/63; Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Bone loss; Bone mass; Bone remodeling; Bone Resorption; Bone turnover; Cancellous bone; Cell death; Gene Knockout Techniques; Humanities and Social Sciences; Inactivation; Metabolism; Mice; Mice, Knockout; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; multidisciplinary; Osteoblastogenesis; Osteoclastogenesis; Osteoclasts; Osteoclasts - physiology; Osteogenesis; Osteoporosis; Osteoprotegerin; Phenotypes; Post-transcription; RNA-Binding Proteins - metabolism; Rodents; Science; TRANCE protein; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep43191

MicroRNAs emerge as critical post-transcriptional regulators in bone metabolism. We have previously reported in vitro that miR-21 promotes osteogenesis, while studies have also revealed miR-21 as a regulator of osteoclastogenesis and a promoter of osteoclast differentiation in vitro . However, in vivo data are still lacking in identifying skeletal function of miR-21, particularly its effects on osteoporosis. Here, using miR-21 knockout (miR-21 −/− ) mice, we investigated effects of miR-21 on bone development, bone remodeling and bone loss. Unexpectedly, miR-21 −/− mice demonstrated normal skeletal phenotype in development and maintained osteoblastogenesis in vivo . Besides, miR-21 −/− mice showed increased receptor activator of nuclear factor κB ligand (RANKL) and decreased osteoprotegerin (OPG) through miR-21 targeting Sprouty 1 (Spry1). Nevertheless, interestingly, miR-21 deficiency promoted trabecular bone mass accrual physiologically. Furthermore, in pathological states, the protection of bone mass was prominent in miR-21 −/− mice. These skeletal effects were attributed to inhibition of bone resorption and osteoclast function by miR-21 deficiency through miR-21 targeting programmed cell death 4 (PDCD4), despite the existence of RANKL. As far as we know, this is the first in vivo evidence of a pro-osteoclastic microRNA. Together, these findings clarified function of miR-21 in bone metabolism, particularly uncovering osteo-protective potential of miR-21 inactivation in osteoporosis.