Downregulation of miR-146a inhibits osteoporosis in the jaws of ovariectomized rats by regulating the Wnt/β-catenin signaling pathway

Abstract

MicroRNAs (miRNAs or miRs) play important roles in osteoporosis and exhibit high potential in the therapeutic treatment of this condition. The present study aimed to explore the effects of miR-146a on bone loss noted in the jawbones of ovariectomized (OVX) rats and the interaction of miR-146a with the Wnt/β-catenin signaling pathway. OVX Sprague-Dawley female rats were used to establish the animal model of osteoporosis (OP). Bone mineral density (BMD) was measured via dual-energy X-ray and the miR-146a levels were detected by reverse transcription-quantitative PCR. miR-146a antagonist (miR-146a-A) and negative control (miR-146a-NC) were used to examine the effects of miR-146a on OVX rats. The contents of osteocalcin and tartrate resistant phosphatase (TRAP) were detected via ELISA. Hematoxylin and eosin, and TRAP staining were used to observe the pathological changes and the number of osteoclasts in the jawbone, respectively. In addition, the expression levels of the nuclear factor of activated T cells c1 (NFATc1), c-Fos and cathepsin K (CTK) in the jawbone were detected by immunohistochemistry, whereas the expression levels of osteoprotegerin, TRAP, dickkopf1, Wnt2 and β-catenin in the same tissues were assessed by western blot analysis. The Wnt2 activator (DKK2-C2) and inhibitor (endostatin) were used to examine the effects of miR-146a on the Wnt/β-catenin pathway. The results indicated that the BMD was increased, whereas the contents of osteocalcin and TRAP were decreased in the miR-146a-A group compared with those noted in the OP or negative control groups (P<0.05). Although the trabecular bone area of the OP group was decreased, the conditions were improved in the miR-146a-A group. The number of osteoclasts was decreased in the miR-146a-A group compared with that noted in the OP group (P<0.05). The expression levels of NFATc1, c-Fos and CTK in the miR-146a-A group were decreased compared with those noted in the OP or negative control groups (P<0.05). Similar results were found following the comparison of the miR-146a-A group with the DKK2-C2 group. Taken together, these data demonstrated that miR-146a downregulation inhibited OP of the jawbone in OVX rats by activating the Wnt/β-catenin signaling pathway.