Compressive Force Inhibits Osteogenic Differentiation of Dental Follicle Stem Cells Through Biglycan/Bone Morphogenetic Protein2/Smad1 Signaling Pathway.

Abstract

This study aimed to investigate the effects and underlying mechanisms of compressive force on the osteogenic differentiation of human dental follicle stem cells (DFSCs) and to explore its potential role in orthodontically induced inflammatory root resorption (OIIRR). Human DFSCs (hDFSCs) were subjected to a compressive force of 2 g/cm². Western blot and quantitative real-time polymerase chain reaction were used to quantify the expression levels of biglycan (BGN), Runt related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and components of the bone morphogenetic protein (BMP)2/Smad1 signaling pathway in hDFSCs. To elucidate the regulatory role of the BGN/BMP2/Smad1 signaling pathway, a BGN overexpression plasmid and a BMP signaling activator were utilized. In addition, a mouse OIIRR model was established to determine the involvement of the BGN/BMP2/Smad1 signaling axis in vivo. Under compressive force, the mRNA and protein expression levels of ALP, RUNX2, and components of the BGN/BMP2/Smad1 signaling pathway were downregulated. Overexpression of BGN significantly upregulated BMP2 and phosphorylated Smad1 expression (P < 0.05) and enhanced the osteogenic differentiation of hDFSCs. Furthermore, activation of the BMP2/Smad1 signaling pathway using sb4 also reversed the compressive force-induced decline in osteogenic differentiation of hDFSCs. In vivo, the expression levels of the BGN/BMP2/Smad1 signaling axis and the osteogenic markers were significantly reduced on the compressive side of periodontal tissue compared with the control group (P < 0.01). BGN plays a crucial role in the osteogenic differentiation of hDFSCs under compressive force via the BMP2/Smad1 signaling axis and may contribute to the occurrence of OIIRR in mice.