Found programs: Anhui Provincial Scientific Research Staffing Plan Project (No. 2022AH050734)
Authors:Song Xinyi, Ding Siqi, Cheng Yuhe, Liu Xiaoyu, Wu Tingting
Keywords:atorvastatin; orthodontic tooth movement; periodontal tissue; bone remodeling; osteogenic differentiation; adult dentin differentiation
DOI:专辑:医药卫生科技
〔Abstract〕 To investigate the effects of atorvastatin (ATV) on the proliferation and differentiation of rat bone marrow mesenchymal stem cells (BMSCs), periodontal ligament stem cells (PDLSCs), and dental pulp stem cells (DPSCs) in vitro, and to validate the regulatory effect of ATV on periodontal bone formation and tooth movement using a rat orthodontic tooth movement (OTM) model. Methods The effects of ATV on the proliferation and osteogenic/odontogenic differentiation of rat BMSCs, PDLSCs, and DPSCs were assessed in vitro. CCK-8 assay was used to detect the proliferation of the three types of cells. Alkaline phosphatase (ALP) staining and Alizarin Red staining were employed to evaluate osteogenic differentiation capacity. Western blot was used to detect the expression of osteogenesis-related proteins [Collagen type I (COL-I), Runt-related transcription factor 2 (Runx2), Bone morphogenetic protein-2 (BMP-2), Osteocalcin (OCN)] and the odontogenesis-related protein Dentin sialophosphoprotein (DSPP) in BMSCs, PDLSCs, and DPSCs. An OTM rat model was established, with rats randomly assigned to an ATV gavage group and a control group. The ATV gavage group received daily oral administration of ATV at a dose of 20 mg/kg, while the control group received an equal volume of solvent. Tooth movement distance was measured via Micro-CT on days 7, 14, and 21. Histomorphology of periodontal tissues was observed using Hematoxylin and Eosin (HE) staining and Masson staining. The gene and protein expression levels of osteogenic markers (BMP-2, Runx2, OCN) on the tension side of the first molar were detected by qRT-PCR and immunohistochemistry, respectively. Results ATV at concentrations of 10⁻⁶ mol/L and 10⁻⁷ mol/L significantly promoted the proliferation and osteogenic/odontogenic differentiation of BMSCs, PDLSCs, and DPSCs, manifested as enhanced ALP activity, increased mineralized nodule formation, and up-regulated expression of osteogenic/odontogenic proteins COL-I, Runx2, BMP-2, OCN, and DSPP (P<0.001). In the OTM model, compared with the control group, the ATV gavage group showed a significant reduction in tooth movement distance (P<0.05), enhanced osteogenic activity in periodontal tissues, and significantly increased gene (P<0.001) and protein (P<0.05) expression of BMP-2, Runx2, and OCN on the tension side of the first molar.