Correlation between various loads and apoptosis in medial platform chondrocytes in knee varus deformity.

Abstract

This study aimed to systematically investigate how different degrees of mechanical loading caused by varying varus angles affect stress distribution and chondrocyte apoptosis in the medial tibial plateau of the knee joint. Specifically, it integrates finite-element analysis to simulate biomechanical stress patterns and evaluates the molecular responses (Piezo1, Bax, Bcl-2, and caspase-3 expressions) to elucidate the mechanobiological interplay contributing to cartilage degeneration. Four knee models with varus angles (6°, 9°, 12°, and 15°) were constructed from computed tomography images. Finite-element analysis was used to evaluate stress distribution and von Mises stress peaks on the medial tibial platform cartilage. Material properties of biological tissues were included. Clinical samples of corresponding varus angles were analyzed for Piezo1, Bax, Bcl-2, and caspase-3 expression using immunofluorescence and histochemistry. The von Mises stress peak contact area of the medial tibial plateau cartilage significantly decreased with increasing varus deformity (p < 0.05), and Piezo1 expression increased with stress load. Elevated Piezo1 expression was associated with significantly higher levels of Bax, Bcl-2, and caspase-3 (p < 0.05). Pathological mechanical loading accelerates chondrocyte apoptosis via the endogenous apoptotic pathway, promoting the progression of knee osteoarthritis. These findings highlight Piezo1 as a potential therapeutic target for managing stress-induced cartilage degeneration.