| First Author | Hu CH | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 43191 | PubMed ID | 28240263 |
| Mgi Jnum | J:274464 | Mgi Id | MGI:6296248 |
| Doi | 10.1038/srep43191 | Citation | Hu CH, et al. (2017) miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice. Sci Rep 7:43191 |
| abstractText | 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 kappaB 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. |
