阿伐他汀激活wnt/β-catenin信号通路促进骨质疏松模型大鼠移植物的骨整合（英文）  

Atorvastatin promotes implant osseointegration via the activation of Wnt/β-catenin signal pathway in osteoporotic rats

作　　者：梁耀中[1] 陈舒[2] 杨裕豪 蓝春海 张国威[1] 纪志盛[1] 林宏生[1] 

机构地区：[1]暨南大学附属第一医院骨科,广东省广州市510630 [2]暨南大学附属第一医院妇产科,广东省广州市510630

出　　处：《中国组织工程研究》2016年第20期2940-2948,共9页Chinese Journal of Tissue Engineering Research

基　　金：the Natural Science Foundation of Guangdong Province,China,No.2014A030313357~~

摘　　要：背景:最近研究报道阿伐他汀可减少骨流失和骨折,但其对移植物骨整合的影响尚未可知。目的:探讨阿伐他汀在骨质疏松症动物模型中对移植性骨整合的作用及相关作用机制。方法:将48只SD大鼠随机分为假手术组,卵巢切除组,10,20 mg/(kg·d)阿伐他汀治疗组。除假手术组外,其他各组均进行卵巢切除手术和骨移植。干预12周后检测各组大鼠椎骨骨密度,移植物骨整合率及移植物抗拔强度。另外,用阿伐他汀处理大鼠的成骨细胞,酶联免疫法检测细胞中骨形成及骨吸收生物指标的表达情况,RT-PCR检测wnt信号通路相关基因的mRNA表达水平。结果与结论:20 mg/(kg·d)阿伐他汀治疗组大鼠的骨密度、骨整合率及移植物抗拔强度均明显高于卵巢切除组(P<0.05)。用阿伐他汀处理的大鼠成骨细胞中碱性磷酸酶、骨钙蛋白及骨保护素表达水平明显升高(P<0.05),破骨细胞分化因子核因子κB受体活化因子配体的表达显著降低(P<0.05)。阿伐他汀治疗组明显提高低密度脂蛋白相关蛋白5和连环蛋白的mRNA表达(P<0.05),抑制Wnt信号通路抑制剂DKK1和骨硬化蛋白Sost的表达(P<0.05)。结果证实,阿伐他汀可通过上调Wnt/β-catenin信号通路,促进骨质疏松模型大鼠移植物的骨整合。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. All rats received ovariectomy and implant surgery except those in the sham-surgery group. Bone mineral density of the lumbar vertebra, osseointegration ratio and pull-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-related gene expression was detected by RT-PCR. RESULTS AND CONCLUSION： Bone mineral density, osseointegration ratio and pull-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, osteocalcin and osteoprotegerin were significantly increased in osteoblasts treated with atorvastatin in vitro（P〈0.05）, and the level of osteoclast differentiation factor RANKL was significantly inhibited（P〈0.05）. Meanwhile, atorvastatin significantly promoted the mR NA expression of low-density lipoprotein associated protein 5 and β-catenin, and inhibited the mR NA expression of dickkopf Wnt signal pathway inhibitor 1 and sclerostin. Our results suggest that atorvastatin promotes implant osseointegration in osteoporotic rats by activating Wnt/β-catenin signal pathway.

关 键 词：骨质疏松 卵巢切除术 骨移植 组织工程 组织构建 骨组织工程 阿伐他汀 移植性骨整合 骨质疏松症 高血脂症 碱性磷酸酶 骨保护素 骨钙蛋白 破骨分化因子 Wnt信号通路 广东省自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]