脉冲电磁场对兔膝骨关节炎软骨下骨骨重建的影响

Evidences showed that subchondral bone remodeling plays an important role in osteoarthritis(OA). It has been reported that pulsed electromagnetic fields (PEMFs) can prevent the degeneration of articular cartilage. On basis of the results of our previous studies, we hypothesized that PEMFs can prevent the degeneration of articular cartilage, at least partly, through regulating subchondral bone remodeling. Bone is continuously remodeled in a tightly regulated manner via the bone-resorbing osteoclasts and bone-forming osteoblasts acting in conjunction to maintain bone homeostasis. RANKL/RANK/OPG pathway has been recently characterized as the final common pathway of osteoclastogenesis and activation of osteoclast. Previous studies have demonstrated that Wnt/β-catenin signaling pathway plays key roles in the regulation of bone growth and remodeling. The objective of this study will be to investigate the possible mechanisms by which PEMFs prevent and treat osteoarthritis. For this purpose we will examine the effects of PEMFs on cartilage and subchondral bone, and further explored the mRNA and protein expressions for several important components of RANKL/RANK/OPG and Wnt/β-catenin signaling pathways in subchondral bone of anterior cruciate ligament transection(ACLT) rabbits. Understanding of the precise mechanisms by which PEMFs elicit these favorable biological responses can help control osteoarthritis.

基于脉冲电磁场（PEMFs）治疗骨关节炎的有效性和课题组前期研究结果，结合骨关节炎中软骨下骨发生骨重建失衡的研究前沿，课题组提出：调控软骨下骨骨重建是PEMFs治疗骨关节炎的作用机制之一的假说。骨重建包括骨吸收和其耦联的骨形成两方面。RANKL/RANK/OPG 信号通路是各种信号调节骨吸收的最后通路，而在新骨形成过程中, Wnt/β-catenin信号通路起着关键的作用。本项目采用多层次(整体、器官、细胞、分子)和多手段(高分辨MRI、显微CT、流式细胞仪、分子生物学等)相结合的方法，探讨PEMFs对前交叉韧带切断的兔膝骨关节炎动物模型关节软骨、软骨下骨及RANKL/RANK/OPG及Wnt/β-catenin信号通路的基因与蛋白表达的影响，从而阐明PEMFs调控软骨下骨骨重建是PEMFs治疗骨关节炎的作用机制之一，为PEMFs治疗骨关节炎提供全新的科学观点。

对软骨下骨代谢与重建的调节是PEMFs 治疗骨关节炎的作用靶点之一。相偶联的骨形成与骨吸收过程是代谢与重建的基础。本研究通过研究主要发现：1、ACLT后的兔与大鼠膝软骨代谢明显缺损，软骨下骨代谢与重建紊乱，其中骨吸收通路RANKL/RANK/OPG与骨形成Wnt/β –catenin信号异常表达均有参与ACLT兔与大鼠膝骨关节炎模型的生成。2、3.8 mT，8 Hz的PEMFs磁场照射被证实对早期膝OA大鼠软骨下骨微观结构和软骨退化有一定的保护作用。3、PEMFs对软骨的保护作用主要通过抑制软骨凋亡实现。4、分子生物学治疗机制可能通过Wnt/β-catenin 和OPG/RANKL/RANK信号通路保护膝骨关节炎软骨下骨。通过此研究，本课题团队先创性阐明靶向调控软骨代谢与软骨下骨重建是PEMFs治疗骨关节炎的作用机制之一，为PEMFs 治疗骨关节炎提供全新的科学观点。