Osteoclast derived exosomal miR 214 3p inhibits osteoblastic bone formation
Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR 214 3p associates with both elevated serum exosomal miR 214 3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast specific miR 214 3p knock in mice have elevated serum exosomal miR 214 3p and reduced bone formation that is rescued by osteoclast targeted antagomir 214 3p treatment. We further demonstrate that osteoclast derived exosomal miR 214 3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast targeted miR 214 3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast derived exosomal miR 214 3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR 214 3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.
Nature communications