Impact of Abnormal Mechanical Stress on Chondrocyte Death in Osteoarthritis

Abstract

BACKGROUND Knee osteoarthritis (KOA) is a prevalent joint disorder affecting middle-aged and elderly populations, characterized by articular cartilage degeneration. Articular cartilage, composed of chondrocytes and extracellular matrix (ECM), withstands mechanical stress during movement. However, abnormal mechanical loading, particularly overload, disrupts cartilage metabolism, triggering catabolic processes that lead to KOA. This study explores the classification of abnormal mechanical loads, their impact on chondrocytes, and the molecular mechanisms driving microenvironmental changes due to abnormal mechanical stress. MATERIAL AND METHODS A comprehensive literature review was conducted using PUBMED, Web of Science, and Google Scholar, focusing on the past decade. Keywords included "knee osteoarthritis" "mechanical pressure", "mitophagy" and "ferroptosis". After excluding irrelevant studies, relevant literature was synthesized and analyzed to elucidate the molecular mechanisms involved. RESULTS This study links macroscopic mechanical pressure changes to microscopic inflammatory environments in KOA, emphasizing the novel role of external mechanical stress in chondrocyte death, particularly ferroptosis. The research highlights distinct effects of various mechanical stress patterns - compressive, tensile, vibrational, electromagnetic, and fluid shear stress - on chondrocytes. High-risk factors like mechanical stress and inflammation induce chondrocyte apoptosis, autophagy, and ferroptosis, elevate degrading enzymes, degrade collagen, and inhibit ECM synthesis. These microenvironmental changes disrupt the balance between cartilage synthesis and degradation, leading to cartilage degeneration in KOA. CONCLUSIONS Chondrocyte death induced by mechanical pressure, along with cartilage destruction, involves apoptosis, autophagy, ferroptosis, inflammation, and ECM degradation, forming a complex signaling network. The activation of the Piezo1 protein is pivotal in these processes, suggesting that targeting Piezo1-mediated pathways under mechanical stimulation may offer promising therapeutic strategies for KOA.

Topics & Concepts