Compressive Force During Orthodontic Tooth Movement Triggers Ferroptosis and Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells Through SCD1 Downregulation

Improper orthodontic treatment can disrupt alveolar bone remodeling, leading to excessive alveolar bone resorption and complications such as bone fenestration and dehiscence. Although ferroptosis has emerged as an important regulator of bone metabolism, its role in mechanical force-induced periodontal tissue remodeling during orthodontic tooth movement (OTM) remains incompletely understood. This study investigated whether ferroptosis regulates the osteogenic response of human periodontal ligament stem cells (hPDLSCs) under compressive force (CF), focusing on stearoyl-CoA desaturase 1 (SCD1). hPDLSCs were subjected to static CF, and RNA sequencing, RT–qPCR, Western blotting, and immunofluorescence were performed to analyze SREBP1 and SCD1 expression. Ferroptosis-related alterations were evaluated using biochemical and mitochondrial analyses. Ferrostatin-1 (Fer-1) rescue, SCD1 knockdown/overexpression, and a rat OTM model were used for functional validation. Prolonged CF downregulated SREBP1 and SCD1 expression, accompanied by ferroptosis-associated alterations and reduced RUNX2 and OPN expression. Fer-1 alleviated these changes, whereas SCD1 overexpression partially restored osteogenic markers and SCD1 knockdown further impaired osteogenic responses. In vivo, SREBP1 and SCD1 expression were reduced on the compression side. Collectively, these findings identify SCD1 as an important regulator linking CF-induced ferroptosis-associated alterations with impaired osteogenic differentiation of hPDLSCs, suggesting SCD1 as a potential target for orthodontic bone remodeling.