ADAMTS2 Mediates Osteogenic Differentiation of Dental Follicle Stem Cells Under Compressive Stress and Inflammation

This study investigates the effects of inflammation and orthodontic forces on the osteogenic differentiation of human dental follicle stem cells (hDFSCs) and their role in periodontal regeneration during orthodontic tooth movement (OTM) in periodontitis patients. Human DFSCs were exposed to interleukin-1β (IL-1β) and orthodontic compressive force (OCF). Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assessed the expression of a disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2), osteogenic markers, and ERK signaling components. ADAMTS2 overexpression (OE) plasmids and ERK activators were applied to explore the ADAMTS2/ERK signaling axis. A mouse periodontitis model with OTM was developed for in vivo evaluation. IL-1β and OCF downregulated ALP, RUNX2, and ERK pathway-related proteins and decreased ADAMTS2 expression. OE of ADAMTS2 significantly enhanced ERK phosphorylation ( P < 0.05), promoting osteogenic differentiation of hDFSCs. ERK pathway activation with C16-PAF partially reversed the suppression of osteogenic differentiation induced by IL-1β and OCF. ADAMTS2/ERK axis components and osteogenic markers were reduced on the compressed side of periodontal tissues in the PD+OTM group ( P < 0.05). These findings suggest that ADAMTS2 regulates the osteogenic differentiation of hDFSCs via the ERK signaling pathway under IL-1β and OCF stimulation, highlighting its potential as a therapeutic target for alveolar bone regeneration during OTM in periodontitis patients.