Role of Acetylcholinesterase in Cartilage Homeostasis and Osteoarthritis

Osteoarthritis (OA) is a multifactorial degenerative disease characterized by chronic inflammation and joint degeneration. Acetylcholinesterase (AChE), a key enzyme in the cholinergic system, plays a crucial role in regulating anti-inflammatory signalling pathways. Disruptions in the cholinergic system, including AChE dysfunction, have been implicated in OA. To investigate the role of AChE in OA, we employed a transgenic mouse model with conditional AChE knockout in articular chondrocytes to examine the effects of reduced AChE expression on inflammatory cytokine levels and knee OA progression. Additionally, we further validated our findings by pharmaceutical inhibition of AChE. Our results demonstrate a significant association between AChE and alpha7 nicotinic receptor expression in knee OA chondrocytes. Conditional knockout of AChE in transgenic mice led to reduced inflammatory cytokine levels and alleviated knee OA symptoms. AChE inhibitors showing promise in managing OA-related inflammation. Our study highlights the critical role of AChE in the pathogenesis of OA and suggests that targeting AChE may offer a novel therapeutic strategy for managing knee OA. By modulating AChE activity, we may be able to regulate anti-inflammatory signaling pathways and alleviate disease progression. These findings have significant implications for the development of innovative treatments for OA, and warrant further investigation into the therapeutic potential of AChE inhibitors and vagus nerve stimulation.