High cholesterol diet increases osteoporosis risk via nhibiting bone formation in rats  

作　　者：Li YOU Zheng-yan SHENG Chuan-ling TANG Lin CHEN Ling PAN Jin-yu CHEN 

机构地区：[1]Department of Osteoporosis, Shanghai First People＇s Hospital, Shanghai Jiaotong University, Shanghai 200080, China [2]Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China

出　　处：《Acta Pharmacologica Sinica》2011年第12期1498-1504,共7页中国药理学报（英文版）

摘　　要：Aim： To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Methods： Female Sprague-Dawley rats were randomly separated into 3 groups： （1） the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; （2） ovariectomised （OVX） rats were bilaterally ovariectomised and fed a standard diet; and （3） the control rats were fed the standard diet. Bone mineral density （BMD） of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol （E2）, osteocalcin （BGP） and carboxy-terminal collagen crosslinks （CTX） were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells （MC3T3-E1） were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. Results： In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta （TGF-β）/bone morphogenic protein （BMP） and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol （12.5-50 pg/mL） inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentra- tion-dependently reduced the expression of BMP2 and Cbfal, and increased the oxidative injury in MC3T3-E1 cells. Conclusion�Aim： To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Methods： Female Sprague-Dawley rats were randomly separated into 3 groups： （1） the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; （2） ovariectomised （OVX） rats were bilaterally ovariectomised and fed a standard diet; and （3） the control rats were fed the standard diet. Bone mineral density （BMD） of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol （E2）, osteocalcin （BGP） and carboxy-terminal collagen crosslinks （CTX） were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells （MC3T3-E1） were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. Results： In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta （TGF-β）/bone morphogenic protein （BMP） and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol （12.5-50 pg/mL） inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentra- tion-dependently reduced the expression of BMP2 and Cbfal, and increased the oxidative injury in MC3T3-E1 cells. Conclusion�

关 键 词：high cholesterol diet HYPERCHOLESTEROLAEMIA OSTEOPOROSIS OSTEOBLASTS oxidative stress bone morphogenic protein 

分 类 号：Q581[生物学—生物化学] S858.317.1[农业科学—临床兽医学]