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miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1

 Kyoung Min Kim  ;  Su Jin Park  ;  Seung-Hyun Jung  ;  Eun Jin Kim  ;  Gadi Jogeswar  ;  Jami Ajita  ;  Yumie Rhee  ;  Cheol-Hee Kim  ;  Sung-Kil Lim 
 Journal of Bone and Mineral Research, Vol.27(8) : 1669-1679, 2012 
Journal Title
 Journal of Bone and Mineral Research 
Issue Date
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.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Endocrinology (내분비연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
가디죠게스(Gadi, Jogeswar)
김경민(Kim, Kyung Min)
김은진(Kim, Eun Jin)
박수진(Park, Su Jin)
아지타자미(Ajita Jami)
이유미(Rhee, Yumie) ORCID logo https://orcid.org/0000-0003-4227-5638
임승길(Lim, Sung Kil)
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