Dpscs Modulate Synovial Macrophage Polarization And Efferocytosis Via Mitophagy

This study investigates the regulatory and reparative capabilities of dental pulp stem cells (DPSCs) on synovitis in temporomandibular joint osteoarthritis (TMJOA) rat models. It elucidates their specific mechanisms of action on synovial macrophages. Sprague-Dawley rats were divided into control, OA, and DPSCs treatment groups. A TMJ arthritis model was induced using monosodium iodoacetate (MIA) and complete Freund's adjuvant (CFA). DPSCs were injected weekly into the TMJs for 4 weeks. Synovitis repair was evaluated using histology analysis. In vitro, a co-culture system of M1-polarized macrophages with DPSCs was established. Effects on macrophage polarization and efferocytosis were assessed using various techniques including mRFP-GFP-LC3 lentivirus transfection, Mito-Tracker Red and Lyso-Tracker Green staining, transmission electron microscopy, and Western blot. In the rat model, DPSCs reduced cell infiltration and collagen deposition, increased anti-inflammatory CD206, decreased inflammatory CD86, and enhanced macrophage phagocytosis of apoptotic cells. DPSCs upregulated autophagosome expression, promoted co-localization with mitochondria and lysosomes, and modulated mitochondrial mitophagy proteins in M1 macrophages. Inhibition of mitophagy partially attenuated the M2 polarization effect and phagocytosis induced by DPSCs. DPSCs effectively reduce M1-polarized macrophage infiltration, promote M2-polarized macrophages, and enhance efferocytosis by promoting mitochondrial autophagy, providing a novel therapeutic strategy for TMJOA synovitis.