Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity.

Abstract

Dental implants have become a widely accepted and successful treatment for fully and partially edentulous patients. Simvastatin has been applied to improve and accelerate the osseointegration of implants by increasing the quantity and quality of bone tissue. However, its potential mechanism has not been elucidated completely. Here, we found that simvastatin significantly enhanced the autophagy level of jaw-derived bone marrow stromal cells (BMSCs) and alleviated production of reactive oxygen species under unfavourable conditions. Simvastatin promoted osteogenic differentiation of BMSCs via enhanced autophagy. Furthermore, simvastatin inhibited the bone resorption activity of osteoclasts. With the use of a rat model of oral implant osseointegration, we found local injection of simvastatin displayed more new bone formation at the interface of the bone and implant compared with that of oral administration. Fluorochrome labelling histomorphometrical analysis and micro-CT also showed that simvastatin promoted the osseointegration of implants. Notably, fewer activated osteoclasts were observed in the region of osseointegration of implants from the simvastatin treatment groups, especially the local delivery of simvastatin. Collectively, our results revealed that simvastatin can increase osteoblastic differentiation of BMSCs via enhanced autophagy and decreased osteoclast activity. Thus, simvastatin could be a viable and promising drug to improve and even accelerate the osseointegration of a dental implant.