递增负荷跑台运动抑制骨质疏松小鼠miR-214表达进而促进骨生成的作用研究

Incremental Load Treadmill Exercise Promotes Bone Formation by Inhibiting miR-214 Expression in Osteoporosis Mice

适宜的运动可促进骨生成,抑制骨吸收,提高机体的骨密度和骨强度,进而起到防治骨质疏松的作用,但到目前为止运动防治骨质疏松的作用机制尚未完全明确。miR-214已被证明参与调控骨代谢,然而其是否参与运动防治骨质疏松的过程,尚缺乏相关的探究。该研究采用去卵巢手术建立骨质疏松小鼠模型,24只12周龄雌性C57BL/6小鼠,随机分为四组:去卵巢组(OVX,n=6)、去卵巢+运动组(OVX+EX,n=6)、假手术组(SHAM,n=6)和假手术+运动组(SHAM+EX,n=6),术后4周进行为期9周的跑台运动干预,最后一次干预结束48 h后取材。进行骨密度(bone mineral density,BMD)、microCT、骨生物力学以及成熟mi R-214、β连环蛋白(β-catenin)、激活转录因子4(activated transcription factor 4,ATF4)、runt相关转录因子2(runt-related transcription factor 2,Runx2)表达的检测。该研究证实,去除卵巢后小鼠的BMD和骨强度均下降,miR-214的表达显著增加,Runx2的表达显著降低。同时其下游靶基因β-catenin和ATF4的蛋白表达也均显著减少。而跑台运动则可以部分逆转上述现象,显著增加去卵巢(ovariectomized,OVX)小鼠和SHAM小鼠的BMD和骨强度,抑制miR-214的表达。该研究提示跑台运动可显著抑制miR-214的表达,同时使miR-214下游靶基因ATF4和β-catenin的蛋白表达增加,进而提高骨质疏松小鼠的BMD和骨强度,部分逆转雌激素丢失导致的骨质流失。

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 C57 BL/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 andβ-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.