Incremental Load Treadmill Exercise Promotes Bone Formation by Inhibiting miR-214 Expression in Osteoporosis Mice
GUO Jianmin1, ZHOU Xuchang1, CHEN Xi1,2, ZHANG Miao1, LI Hui1, ZOU Jun1*
Accumulating evidence showed that appropriate exercise can promote bone formation and inhibit bone resorption to increase bone density and bone strength, thus playing a role in the prevention and treatment of osteoporosis. However, the specific mechanism has not been fully understood. miR-214 has been shown to be involved in the regulation of bone metabolism. However, whether miR-214 mediates the process of preventing and treating osteoporosis has not been revealed. In this study, the osteoporosis mouse model was established by ovariectomy. Twelve-week-old female C57BL/6 mice were randomly divided into four groups: ovariectomized group (OVX, n=6), ovariectomized+exercise group (OVX+EX, n=6), sham operation group (SHAM, n=6) and sham operation+exercise group (SHAM+EX, n=6). The two exercise groups were performed 9 weeks of treadmill running exercise after four weeks of operation. All the mice were sacrificed 48 h after the end of the last intervention. The results showed that both bone density and bone strength decreased after ovariectomy in mice. The expression of miR-214 was significantly increased, while the expression of Runx2, β-catenin, and ATF4 were significantly decreased in OVX mice when compared to the SHAM mice. And treadmill exercise can increase the bone mineral density (BMD) and bone strength of the OVX and SHAM mice. We also found that treadmill exercise can significantly inhibit the expression of miR-214 in OVX mice, and the protein expression of its downstream target genes ATF4 and β-catenin were significantly increased. In conclusion, exercise may increase bone formation in osteoporotic mice and partially reverse the estrogen defect induced bone loss by inhibiting the expression of miR-214.
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