Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK

Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18â 25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In the present study, we detected the expression pattern of 10 miRNAs in patient serum samples, and identified six miRNAs altered expression in patients with osteoporosis relative to non-osteoporosis. We selected miR-144-3p for further investigation, and showed that it regulates osteoclastogenesis by targeting RANK and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p in CD14+ PBMCs changed TRAP activity and the osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP stainingďź CCK-8 and flow cytometry analyses revealed that miR-144-3p also affects osteoclast formation, proliferation and apoptosis. Together, these results indicate that miR-144-3p critically mediates bone homeostasis, and thus, represents a promising novel therapeutic candidate for the treatment of this disease.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author