COX-2通过激活感觉神经的PGE2受体4（EP4）促进软骨下骨成骨从而导致 骨关节炎的机制研究

骨关节炎(OA)是最常见的关节炎类型，具有明显的软骨退行性改变，然而直接针对软骨的治疗并不是很理想。在关节运动时，软骨下骨给关节软骨提供机械性支撑,软骨下骨的结构改变会引起关节软骨的病理变化，从而导致骨关节炎的发生。环氧化酶COX-2是前列腺素合成过程中的关键限速酶。许多文献报道提示软骨来源的COX-2参与OA的疾病进展。然而，关于软骨下骨中骨细胞分泌的COX-2在骨关节炎中的作用尚未明确。. 另外，感觉神经已被证实能够感受骨密度、机械应力以及代谢的变化，从而调控骨稳态。新的研究表明，COX-2的活性产物PGE2通过刺激感觉神经促进下丘脑五羟色胺信号通路来调控成骨细胞成骨。本研究拟探讨探究软骨下骨中COX-2是否通过激活感觉神经，引起中枢五羟色胺信号通路的变化从而调控骨代谢，并解析COX-2信号通路在骨关节炎发病机制中的作用，为进一步防治骨关节炎提供新思路。

Osteoarthritis (OA) is the most common form of arthritis, all of which have degenerative changes in cartilage. However, the treatment directly targeting cartilage is not ideal. During the joint movement, the subchondral bone provides mechanical support for the articular cartilage. Therefore, the structural changes of the subchondral bone can cause pathological changes of articular cartilage, leading to the occurrence of arthritis. Cyclooxygenase (COX)-2 is a key rate-limiting enzyme during the synthesis of prostaglandins and is expressed in both bone tissue and bone cells. It has been reported that COX-2 was significantly increased in the articular cartilage of OA patients, suggesting that chondrocyte-derived COX-2 is involved in OA disease progression. However, the role of osteocyte-derived COX-2 in the subchondral bone in arthritic cartilage degeneration is not yet clear..In addition, sensory nerves have been proved to modulate bone homeostasis by sensing changes in bone density, mechanical stress, and metabolism. Recent research suggests that PGE2, the active product of COX-2, regulates osteogenesis of osteoblasts by stimulating sensory nerves to promote the hypothalamic serotonin signaling pathway. Our study aims to explore whether COX-2 in subchondral bone can regulate bone metabolism by activating sensory nerves and causing changes in central serotonin signaling pathway, and to analyze the role of COX-2 signaling pathway in the pathogenesis of osteoarthritis, so as to provide new strategy for prevention and treatment of osteoarthritis.