BoneKEy Reports | BoneKEy Watch

MicroRNAs identified that regulate osteoblast differentiation



DOI:10.1038/bonekey.2012.132

MicroRNAs are small noncoding RNAs that inhibit target gene expression; two such miRNAs, miR-34b and miR-34c, were investigated by Wei et al. for their role in osteoblast proliferation/differentiation. In vitro studies showed that levels of both miRs 34-b and 34-c increased 1.8 times during 21 days of culture, the time taken for full osteoblast differentiation. Levels of miR-34-a also increased, but only slightly. Expression of 34-b and 34-c was highly restricted to osteoblasts; the distribution of 34-a was more general.

In vivo experiments in transgenic mice showed overexpression of miR-34-c in osteoblasts, revealing that these animals had a lower bone mass than wild type mice, with a clear reduction in mineralized bone volume in the vertebrae. Osteoblast number and bone formation rate were also reduced.

The authors showed that the two miRs exerted their effect by inhibition of osteoblast proliferation, mediated by suppression of CDK4, CDK6 and Cyclin D. Terminal differentiation of osteoblasts was also inhibited by blocking of SATB2, a nuclear matrix protein known to be critical in the differentiation of osteoblasts.

Editor's comment: This is the first in vivo demonstration that osteoblast-specific inactivation of miRs 34-b and 34-c enhances bone formation. Because miR34 s do not affect Wnt signaling or bone resorption, their inactivation could be a new therapeutic target for increasing bone formation.


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