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Micro RNA-214 responsible for reduced bone formation in osteoporotic elderly patients
Wang et al. provide the first evidence for a pathophysiological role for a microRNA (miRNA) molecule in elderly patients with osteoporosis.
Analysis of miRNAs in nine healthy adults and in 40 elderly osteoporotic patients with fractures revealed that one miRNA in particular, miR-214, was present in higher amounts in the bones of the aged individuals. The highest levels of miR-214 were observed in the patients who had reduced expression of the genes encoding the bone formation markers osteocalcin and alkaline phosphatase.
Experiments using mouse preosteoblast MC3T3-E1 cells treated with either an miR-214 agonist or antagonist revealed that miR-214 is able to inhibit matrix mineralization and osteoblast activity. It directly targets ATF4, a gene that regulates osteoblast activity. In vivo studies also revealed that miR-214 inhibited bone formation and that an miR-214 antagonist in estrogen-depleted mice, 6 months after they had been ovariectomized (OVX), prevented the development of osteoporosis. Trabecular bone mass and architecture showed substantial improvements in the OVX mice treated with the miR-214 antagonist.
Editor’s comment: miRNA-214 is present in osteoblasts and acts to inhibit bone formation under various pathophysiological and physiological scenarios. A therapeutic blockage of miRNA-214 could be helpful in the control of osteoporosis in post-menopausal women and in elderly patients of both sexes.
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