Osteogenic growth peptide enhances the proliferation of bone marrow mesenchymal stem cells from osteoprotegerin-deficient mice by CDK2/cyclin A

被引:39
作者
Fei, Qinming [1 ]
Guo, Changjun [1 ]
Xu, Xiaoya [2 ]
Gao, Jianjun [2 ]
Zhang, Jian [1 ]
Chen, Tongyi [1 ]
Cui, Dafu [3 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Orthopaed Surg, Shanghai 200032, Peoples R China
[2] Fudan Univ, Inst Radiat Med, Dept Bone Metab, Shanghai 200032, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
关键词
osteogenic growth peptide; osteoprotegerin; mesenchymal stem cell; cell proliferation; CDK2; cyclin A; DIFFERENTIATION; OSTEOPOROSIS; CULTURES;
D O I
10.1093/abbs/gmq086
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To promote bone formation is one of the fundamental strategies in osteoporosis treatment and fractures repair. As one of the stimulators on bone formation, osteogenic growth peptide (OGP) increases both proliferation and differentiation of the osteoblasts in vitro and in vivo, in which osteoprotegerin (OPG) has been suggested being involved. In this study, we evaluated the effects of OGP on bone marrow mesenchymal stem cells (MSCs) from OPG-deficient mice in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, alkaline phosphatase (ALP) activity assay, real-time polymerase chain reaction, and western blot analysis. Results showed that OGP stimulated MSC proliferation and increased the expression of CDK2 and cyclin A in MSCs both at mRNA and protein levels. However, no differentiative effect of OGP was shown as ALP activity and the expression levels of Runx2 and Osterix were not increased significantly by OGP. Our study suggested that OGP may increase the bone formation in OPG-deficient mice by stimulating MSC proliferation rather than differentiation, and probably by triggering CDK2/cyclin A pathway.
引用
收藏
页码:801 / 806
页数:6
相关论文
共 28 条
[1]   Osteogenic growth peptide: From concept to drug design [J].
Bab, I ;
Chorev, M .
BIOPOLYMERS, 2002, 66 (01) :33-48
[2]   HISTONE H4-RELATED OSTEOGENIC GROWTH PEPTIDE (OGP) - A NOVEL CIRCULATING STIMULATOR OF OSTEOBLASTIC ACTIVITY [J].
BAB, I ;
GAZIT, D ;
CHOREV, M ;
MUHLRAD, A ;
SHTEYER, A ;
GREENBERG, Z ;
NAMDAR, M ;
KAHN, A .
EMBO JOURNAL, 1992, 11 (05) :1867-1873
[3]   Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats [J].
Brager, MA ;
Patterson, MJ ;
Connolly, JF ;
Nevo, Z .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2000, 18 (01) :133-139
[4]   osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification [J].
Bucay, N ;
Sarosi, I ;
Dunstan, CR ;
Morony, S ;
Tarpley, J ;
Capparelli, C ;
Scully, S ;
Tan, HL ;
Xu, WL ;
Lacey, DL ;
Boyle, WJ ;
Simonet, WS .
GENES & DEVELOPMENT, 1998, 12 (09) :1260-1268
[5]   Osteogenic growth peptide C-terminal pentapeptide [OGP(10-14)] acts on rat bone marrow mesenchymal stem cells to promote differentiation to osteoblasts and to inhibit differentiation to adipocytes [J].
Chen, Zhi-xin ;
Chang, Min ;
Peng, Ya-li ;
Zhao, Li ;
Zhan, Yu-rui ;
Wang, Li-jing ;
Wang, Rui .
REGULATORY PEPTIDES, 2007, 142 (1-2) :16-23
[6]  
CHEN ZX, 2007, THESIS FUDAN U
[7]   Truncated human LMP-1 triggers differentiation of C2C12 cells to an osteoblastic phenotype in vitro [J].
Fei, Qinming ;
Boden, Scott D. ;
Sangadala, Sreedhara ;
Viggeswarapu, Manjula ;
Liu, Yunshan ;
Titus, Louisa .
ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2007, 39 (09) :693-700
[8]  
[费琴明 Fei Qinming], 2002, [中华骨科杂志, Chinese Journal of Orthopedics], V22, P165
[9]  
Fei QM, 2001, ACTA BIOCH BIOPH SIN, V33, P415
[10]   Osteogenic growth peptide modulates fracture callus structural and mechanical properties [J].
Gabet, Y ;
Müller, R ;
Regev, E ;
Sela, J ;
Shteyer, A ;
Salisbury, K ;
Chorev, M ;
Bab, I .
BONE, 2004, 35 (01) :65-73