Osr2 Regulates Autophagy To Mediate Cementoblast Compression-Induced Root Resorption

Orthodontically Induced Inflammatory Root Resorption remains a prevalent complication in orthodontic treatment, leading to tooth root damage and compromised dental health. Despite progress in orthodontic methods, the molecular mechanisms underpinning root resorption, particularly the role of key regulators like OSR2, are not fully understood. Previous studies suggest mechanical stress in cementoblasts contributes to OIIRR, but the specific pathways remain unclear. This study investigates the role of OSR2 in mediating apoptosis and osteoclastogenesis during orthodontic tooth movement (OTM) and explores how autophagy may regulate these processes. We developed both in vitro and in vivo models to study OSR2′s role under compressive stress. In vitro, OCCM-30 cells were subjected to compression, while an OTM rat model was used for in vivo analysis. OSR2-overexpressing OCCM cells were treated with rapamycin to evaluate autophagy’s role. Gene and protein expression levels were measured through qRT-PCR, Western blotting, immunofluorescence, and flow cytometry. Additionally, we analyzed osteoclast differentiation and cytokine profiles. The results showed that OSR2 expression was significantly upregulated under compressive force, correlating with increased apoptosis and osteoclastogenesis. OSR2 overexpression promoted cell apoptosis, reduced viability, and enhanced osteoclastic differentiation in vitro. In vivo, rapamycin treatment activated autophagy, reduced OSR2-mediated apoptosis, and decreased root resorption in rats subjected to OTM. This study identifies OSR2 as a key regulator of apoptosis and osteoclastogenesis in cementoblasts during OTM, mediated through autophagy inhibition. Activating autophagy can mitigate these effects, offering potential therapeutic strategies to control root resorption in orthodontic treatments.