microRNA-210 is involved in the regulation of postmenopausal osteoporosis through promotion of VEGF expression and osteoblast differentiation

被引:141
作者
Liu, Xiao-Dong [1 ]
Cai, Feng [1 ]
Liu, Liang [1 ]
Zhang, Yan [1 ]
Yang, An-Li [1 ]
机构
[1] Tongji Univ, Sch Med, Dept Orthoped, YangPu Hosp, Shanghai 200090, Peoples R China
基金
中国国家自然科学基金;
关键词
BMSC differentiation; miR-210; postmenopausal osteoporosis; VEGF; BONE METABOLISM; GENE-EXPRESSION; SEX STEROIDS; VASCULAR INTEGRITY; TRABECULAR BONE; BREAST-CANCER; HYPOXIA; CELLS; ANGIOGENESIS; MECHANISMS;
D O I
10.1515/hsz-2014-0268
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
MicroRNAs (miRNAs) are small non-protein-codingRNAs that function as negative gene expression regulators. miRNA-210 (miR-210) has recently been recognized in the pathogenesis of osteonecrosis associated with angiogenesis. Herein we aimed to explore the clinical significance of miR-210 treatment for postmenopausal osteoporosis. The expression of miR-210 was detected in bone marrow mesenchymal stem cells (BMSCs) in vitro and miR-210 significantly promoted the expression of vascular edothelial growth factor (VEGF) in BMSCs in a time-dependent manner (p < 0.05). And miR-210 suppressed PPAR. expression but increased the expression of ALP and osterix, demonstrating that miR-210 inhibited adipocyte differentiation and promoted osteoblast differentiation of BMSCs in vitro. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and VEGF in 17 beta-estradiol (E2) treated osteoblasts were significantly increased in a dose- and time-dependent manner (p < 0.05). And E2 inducted the VEGF expression through the PI3K/AKT signaling pathway in osteoblasts. Taken together, these data implied that miR-210 played an important role in ameliorating the estrogen deficiency caused-postmenopausal osteoporosis through promotion the VEGF expression and osteoblast differentiation.
引用
收藏
页码:339 / 347
页数:9
相关论文
共 50 条
[1]
The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]
MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]
Bonnick SL, 2010, MENOPAUSE, V17, P25, DOI [10.1097/gme.0b013e3181c617e6, 10.1097/gme.0b013e3181e617e6]
[4]
CHANGES IN TRABECULAR BONE, HEMATOPOIESIS AND BONE-MARROW VESSELS IN APLASTIC-ANEMIA, PRIMARY OSTEOPOROSIS, AND OLD-AGE - A COMPARATIVE HISTOMORPHOMETRIC STUDY [J].
BURKHARDT, R ;
KETTNER, G ;
BOHM, W ;
SCHMIDMEIER, M ;
SCHLAG, R ;
FRISCH, B ;
MALLMANN, B ;
EISENMENGER, W ;
GILG, T .
BONE, 1987, 8 (03) :157-164
[5]
hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer [J].
Camps, Carme ;
Buffa, Francesca M. ;
Colella, Stefano ;
Moore, John ;
Sotiriou, Christos ;
Sheldon, Helen ;
Harris, Adrian L. ;
Gleadle, Jonathan M. ;
Ragoussis, Jiannis .
CLINICAL CANCER RESEARCH, 2008, 14 (05) :1340-1348
[6]
MicroRNA Regulation of DNA Repair Gene Expression in Hypoxic Stress [J].
Crosby, Meredith E. ;
Kulshreshtha, Ritu ;
Ivan, Mircea ;
Glazer, Peter M. .
CANCER RESEARCH, 2009, 69 (03) :1221-1229
[7]
Reduced local blood supply to the tibial metaphysis is associated with ovariectomy-induced osteoporosis in mice [J].
Ding, Wen-Ge ;
Wei, Zhao-Xiang ;
Liu, Jin-Bo .
CONNECTIVE TISSUE RESEARCH, 2011, 52 (01) :25-29
[8]
Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis [J].
Ell, Brian ;
Mercatali, Laura ;
Ibrahim, Toni ;
Campbell, Neil ;
Schwarzenbach, Heidi ;
Pantel, Klaus ;
Amadori, Dino ;
Kang, Yibin .
CANCER CELL, 2013, 24 (04) :542-556
[9]
Estradiol-Treated Mesenchymal Stem Cells Improve Myocardial Recovery After Ischemia [J].
Erwin, Graham S. ;
Crisostomo, Paul R. ;
Wang, Yue ;
Wang, Meijing ;
Markel, Troy A. ;
Guzman, Mike ;
Sando, Ian C. ;
Sharma, Rahul ;
Meldrum, Daniel R. .
JOURNAL OF SURGICAL RESEARCH, 2009, 152 (02) :319-324
[10]
LONG-TERM ESTROGEN REPLACEMENT THERAPY PREVENTS BONE LOSS AND FRACTURES [J].
ETTINGER, B ;
GENANT, HK ;
CANN, CE .
ANNALS OF INTERNAL MEDICINE, 1985, 102 (03) :319-324