BoneKEy Reports | BoneKEy Watch

Micro RNA 214 is a bone-formation inhibitor



DOI:10.1038/bonekey.2013.56

Wang et al. first assessed some of the micro RNAs (miRNAs) thought to be involved in bone formation and development by looking at their expression in adult femurs. Expression levels of the 33 enriched miRNAs identified were then examined in human bone samples from 40 older people who had sustained fractures. One, miR-214, was shown to be negatively correlated with expression of osteocalcin and alkaline phosphatase in both men and women.

Follow-up mouse studies showed that miR-214 inhibited osteoblast activity and mineral deposition in the bone matrix. miR-214 appeared to regulate osteoblast activity by targeting the Atf4 gene. Two mouse lines showing enhanced expression of miR-214 revealed that the rate of mineral apposition and bone reformation, and the ratio of osteoblast surface to bone surface were all significantly reduced, effectively demonstrating that miR-214 acts via Atf4 to inhibit bone formation.

Blocking miR-214 therapeutically within osteoblasts restored bone formation to normal levels and was shown to reverse some of the effects of osteoporosis in ovariectomized mice.

Editor’s comment: This study highlights the importance of microRNAs in the regulation of bone mass by directly demonstrating their relevance in human specimens and by providing a proof of concept that miR-214 inhibition promotes bone formation in mice with ovariectomy-induced osteoporosis.


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