Atorvastatin promotes implant osseointegrationviathe activation of Wnt/β-catenin signal pathway in osteoporotic rats / 中国组织工程研究

ABSTRACT

BACKGROUND:Atorvastatin has been shown to reduce bone loss and fracture, but its effects on implant osseointegration remain unknown. OBJECTIVE:To investigate the effects of atorvastatin on implant osseointegration in osteoporotic rats and the underlying mechanisms. METHODS:Forty-eight Sprague-Dawley rats were randomized into sham-surgery, ovariectomy, and atorvastatin (10 and 20 mg/kg per day) treatment groups, respectively. Al rats received ovariectomy and implant surgery except those in the sham-surgery group. Bone mineral density of the lumbar vertebra, osseointegration ratio and pul-out strength of implants were measured after 12-week treatment.Levels of bone formation and resorption markers in osteoblasts treated with atorvastatin were determined by ELISA. Wnt pathway-relatedgene expression was detected by RT-PCR. RESULTS AND CONCLUSION:Bone mineral density, osseointegration ratio and pul-out strength of implants were significantly increased in 20 mg/kg per day of atorvastatin treatment group compared with ovariectomy group (P< 0.05). Levels of alkaline phosphatase, osteocalcinand osteoprotegerinwere significantly increased in osteoblasts treated with atorvastatinin vitro(P<0 .05), and the level of osteoclast differentiation factor RANKL was significantly inhibited (P< 0.05). Meanwhile, atorvastatin significantly promoted the mRNA expression of low-density lipoprotein associated protein 5and β-catenin, and inhibited the mRNA expression of dickkopfWnt signal pathway inhibitor 1and sclerostin. Our results suggest that atorvastatin promotes implant osseointegration in osteoporotic rats by activating Wnt/β-catenin signal pathway.