Group authorship/contribution: KMK and SJP contributed equally to this work.
miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1
Version of Record online: 17 JUL 2012
Copyright © 2012 American Society for Bone and Mineral Research
Journal of Bone and Mineral Research
Volume 27, Issue 8, pages 1669–1679, August 2012
How to Cite
Kim, K. M., Park, S. J., Jung, S.-H., Kim, E. J., Jogeswar, G., Ajita, J., Rhee, Y., Kim, C.-H. and Lim, S.-K. (2012), miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1. J Bone Miner Res, 27: 1669–1679. doi: 10.1002/jbmr.1604
- Issue online: 17 JUL 2012
- Version of Record online: 17 JUL 2012
- Accepted manuscript online: 19 MAR 2012 01:38PM EST
- Manuscript Accepted: 5 MAR 2012
- Manuscript Revised: 30 JAN 2012
- Manuscript Received: 4 OCT 2011
- MESENCHYMAL STEM CELL;
Uncontrolled oxidative stress impairs bone formation and induces age-related bone loss in humans. The FoxO family is widely accepted to play an important role in protecting diverse cells from reactive oxygen species (ROS). Activation of FoxO1, the main FoxO in bone, stimulates proliferation and differentiation as well as inhibits apoptosis of osteoblast lineage cells. Despite the important role of FoxO1, little is known about how FoxO1 expression in bone is regulated. Meanwhile, several recent studies reported that microRNAs (miRNAs) could play a role in osteoblast differentiation and bone formation by targeting various transcriptional factors. Here, we identified one additional crucial miRNA, miR-182, which regulates osteoblastogenesis by repressing FoxO1 and thereby negatively affecting osteogenesis. Overexpression of miR-182 in osteoblast lineage cells increased cell apoptosis and inhibited osteoblast differentiation, whereas in vivo overexpression of miR-182 in zebrafish impaired bone formation. From in silico analysis and validation experiments, FoxO1 was identified as the target of miR-182, and restoration of FoxO1 expression in miR-182–overexpressing osteoblasts rescued them from the inhibitory effects of miR-182. These results indicate that miR-182 functions as a FoxO1 inhibitor to antagonize osteoblast proliferation and differentiation, with a subsequent negative effect on osteogenesis. To treat bone aging, an antisense approach targeting miR-182 could be of therapeutic value. © 2012 American Society for Bone and Mineral Research.