Piezo1 induces mitochondrial autophagy dysfunction leading to cartilage injury in knee osteoarthritis

Abstract

Abstract Background External mechanical stress plays a pivotal role in the pathogenesis of knee osteoarthritis. Piezo1 can sense mechanical stress changes on the surface of various cell types and convert them into bioelectrical signals to regulate cellular functions. Therefore, our study aimed to investigate the role of Piezo1 in mechanically induced KOA and elucidate its underlying mechanisms. Methods In this study, we employed various techniques to assess the effects of mechanical stress on knee joint cartilage in vivo and in vitro experiments. In vivo, we performed Micro-CT scanning, H&E staining, and ELISA analysis on the knee joints to evaluate the degree of cartilage damage and the expression of pro-inflammatory factors. In vitro, we utilized a cell stretcher to apply mechanical stress specifically to chondrocytes. Subsequently, we investigated the expression levels of Piezo1, pro-inflammatory factors, Collagen II, and other relevant markers within the chondrocytes. This approach aimed to shed light on the potential impact of Piezo1 on chondrocytes when subjected to mechanical stress. Results Elevated expression of Piezo1 was observed in the cartilage of mice post-treadmill exercise intervention, with noticeable damage to the cartilage tissue and reduced surface smoothness. External mechanical stress significantly lowered the synthesis of the extracellular matrix in chondrocytes, potentially through the inhibition of mitochondrial autophagy levels, leading to increased mitochondrial dysfunction and the induction of pro-apoptotic proteins and pro-inflammatory cytokines. Conclusions Mechanical stress induces extracellular matrix degradation and promotes KOA progression through Piezo1-mediated chondrocyte autophagy dysfunction and apoptotic injury.

Keywords

• Piezo1
• Cartilage
• Mitochondria
• Autophagy
• Knee osteoarthritis