适度机械应力与跑步运动通过抑制RhoA/ROCK/NF-κB通路改善骨关节炎进展

Moderate Mechanical Stress and Treadmill Exercise Improve Osteoarthritis by Inhibiting RhoA/ROCK/NF-κB Pathway

目的研究适度的机械应力和跑步运动通过调控RhoA/ROCK/NF-κB通路治疗骨关节炎的机制与效果。方法在细胞实验方面,通过将不同强度机械应力施加于软骨细胞以研究机械应力对软骨细胞功能和代谢状态的影响。然后用过表达腺病毒或si RNA干预软骨细胞调控ROCK1的表达,从而研究ROCK1基因对软骨细胞代谢和功能的影响。在动物实验中,首先通过将SD大鼠内侧半月板胫骨韧带切断建立内侧半月板不稳定(DMM)模型。通过给予DMM大鼠适度的跑步锻炼方案(15米/分,30分钟/天,5天/周,4周)研究跑步锻炼对骨关节炎进展的影响。结果研究发现过度的机械应力会导致Rho A/ROCK通路的激活。ROCK1在软骨细胞中的过度表达会影响合成代谢和分解代谢平衡以及激活NF-κB通路,从而加重软骨细胞炎症反应。通过si RNA敲减干预和给予适度应力能下调ROCK1表达从而保护软骨细胞和减轻炎症。适度的跑步运动能降低关节软骨中ROCK1的表达从而减轻软骨损伤和软骨下骨重塑。结论适度的机械应力和跑步运动能通过抑制RhoA/ROCK/NF-κB通路改善骨关节炎进展。

Objective To explore the mechanisms and effects of moderate mechanical stress and treadmill exercise improving osteoarthritis(OA)by regulating RhoA/ROCK/NF-κB pathway.Methods In the in vitro experiments which studied the effect of mechanical stress on the function and metabolism,chondrocytes were given the mechanical stress of different intensity.Then,adenovirus(overexpression)or siRNA(knockdown)vectors were used to regulate ROCK1 expression,thus studying the effect of ROCK1 gene on the metabolism and function of chondrocytes.As for in vivo experiments,the model of destabilization of the medial meniscus(DMM)in SD rats was established by cutting the tibial ligament of the medial meniscus.To study the influence of treadmill exercise on the OA progression,moderate treadmill exercise program(15 m/min,30 min/day,5 days/week,4 weeks)was applied to the rat model.Results It was found that excessive mechanical stress could lead to the activation of RhoA/ROCK pathway.The results demonstrated that the overexpression of ROCK1 in chondrocytes could affect the balance of anabolism and catabolism and aggravate the inflammation of chondrocytes by activating NF-κB pathway,while knockdown of ROCK1 by siRNA and moderate mechanical stress could protect chondrocytes and reduce inflammation.Moreover,moderate treadmill exercise reduced the expression of ROCK1 in articular cartilage,thus reducing cartilage damage and subchondral bone loss.Conclusion Moderate mechanical stress and treadmill exercise improve the OA progression by inhibiting the RhoA/ROCK/NF-κB pathway.