Research Progress on the Mechanism of Piezol-Mediated Autophagy and Tuina in Knee Osteoarthritis

Abstract

Knee osteoarthritis (KOA) is a chronic degenerative joint disease defined by articular cartilage breakdown, a process involving “stage-dependent” disruption of chondrocyte autophagy homeostasis. An imbalance in the joint's local mechanical environment acts as a critical initiating factor that disrupts this autophagic homeostasis. The mechanosensitive ion channel Piezo1 is a pivotal molecular hub through which chondrocytes perceive external mechanical signals. By mediating Ca2+ influx and modulating downstream signaling pathways, Piezo1 links mechanical stress to cartilage degeneration through the regulation of autophagy in KOA chondrocytes. As a classic nonpharmacological therapy in traditional Chinese medicine for KOA, Tuina exerts chondroprotective effects by improving joint biomechanics, suppressing inflammation, and regulating cellular signaling. However, whether Tuina directly modulates Piezo1 channel activity to regulate chondrocyte autophagy remains an open question, as direct experimental evidence is currently lacking. This article reviews the structure and function of the Piezo1 channel and its molecular role in mediating mechanical signals to regulate autophagy in KOA chondrocytes. It further summarizes the therapeutic targets of Tuina intervention in KOA and its regulatory effects on autophagy-related pathways, including Piezo1-PI3K/AKT/mTOR. Finally, we propose a “Piezo1-mechanotransduction-autophagy” axis as a working framework and discuss the potential routes through which Tuina may engage this axis. This review aims to provide a theoretical foundation and highlight key directions for future experimental validation, thereby advancing the scientific understanding of Tuina in treating KOA.