Leptin effect on RANKL and OPG expression in MCM-E1 osteoblasts

被引:51
作者
Lamghari, M. [1 ]
Tavares, L. [1 ]
Camboa, N. [1 ]
Barbosa, M. A. [1 ]
机构
[1] Inst Engn Biomed, Lab Biomat, P-4150180 Oporto, Portugal
关键词
osteoblasts; MC3T3-E1; leptin; Ob-Ra; Ob-Rb; RANKL; OPG;
D O I
10.1002/jcb.20853
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
Recent studies have suggested that leptin hormone may play a pivotal role on bone remodeling through a direct effect by modulating positively the OPG/RANKL balance. Here, we investigate the effect of leptin hormone on RANKL and OPG expression in MC3T3-E1 osteoblasts using RT-PCR and ELISA measurements. We have at first identified the expression of Ob-Rb and Ob-Ra leptin receptor isoforms in MC3T3-E1 and observed that these cells respond to mrleptin treatments. We then investigated the effect of mrleptin on RANKL and OPG expression. We show that mrleptin dose-dependently regulated the expression of RANKL mRNA with complete inhibition observed at concentrations higher than 12 ng/ml. This effect was confirmed with sRANKL protein measurements. However, the exposure of MC3T3-E1 to mrleptin had no effect on OPG mRNA. Taken together, these results suggest that leptin modulates positively OPG/RANKL balance by inhibiting the expression of RANKL gene.
引用
收藏
页码:1123 / 1129
页数:7
相关论文
共 28 条
[1]   Leptin reduces ovariectomy-induced bone loss in rats [J].
Burguera, B ;
Hofbauer, LC ;
Thomas, T ;
Gori, F ;
Evans, GL ;
Khosla, S ;
Riggs, BL ;
Turner, RT .
ENDOCRINOLOGY, 2001, 142 (08) :3546-3553
[2]   Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo [J].
Cornish, J ;
Callon, KE ;
Bava, U ;
Lin, C ;
Naot, D ;
Hill, BL ;
Grey, AB ;
Broom, N ;
Myers, DE ;
Nicholson, GC ;
Reid, IR .
JOURNAL OF ENDOCRINOLOGY, 2002, 175 (02) :405-415
[3]   Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass [J].
Ducy, P ;
Amling, M ;
Takeda, S ;
Priemel, M ;
Schilling, AF ;
Beil, FT ;
Shen, JH ;
Vinson, C ;
Rueger, JM ;
Karsenty, G .
CELL, 2000, 100 (02) :197-207
[4]   Leptin regulation of bone resorption by the sympathetic nervous system and CART [J].
Elefteriou, F ;
Ahn, JD ;
Takeda, S ;
Starbuck, M ;
Yang, XL ;
Liu, XY ;
Kondo, H ;
Richards, WG ;
Bannon, TW ;
Noda, M ;
Clement, K ;
Vaisse, C ;
Karsenty, G .
NATURE, 2005, 434 (7032) :514-520
[5]   Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin [J].
Elmquist, JK .
PHYSIOLOGY & BEHAVIOR, 2001, 74 (4-5) :703-708
[6]   Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: Impact on differentiation markers, apoptosis, and osteoclastic signaling [J].
Gordeladze, JO ;
Drevon, CA ;
Syversen, U ;
Reseland, JE .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2002, 85 (04) :825-836
[7]   Leptin inhibits osteoclast generation [J].
Holloway, WR ;
Collier, FM ;
Aitken, CJ ;
Myers, DE ;
Hodge, JM ;
Malakellis, M ;
Gough, TJ ;
Collier, GR ;
Nicholson, GC .
JOURNAL OF BONE AND MINERAL RESEARCH, 2002, 17 (02) :200-209
[8]   Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. [J].
Horwood, NJ ;
Elliott, J ;
Martin, TJ ;
Gillespie, MT .
ENDOCRINOLOGY, 1998, 139 (11) :4743-4746
[9]   Vector-averaged gravity regulates gene expression of receptor activator of NF-κB (RANK) ligand and osteoprotegerin in bone marrow stromal cells via cyclic AMP/protein kinase A pathway [J].
Kanematsu, M ;
Yoshimura, K ;
Takaoki, M ;
Sato, A .
BONE, 2002, 30 (04) :553-558
[10]   Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation [J].
Lacey, DL ;
Timms, E ;
Tan, HL ;
Kelley, MJ ;
Dunstan, CR ;
Burgess, T ;
Elliott, R ;
Colombero, A ;
Elliott, G ;
Scully, S ;
Hsu, H ;
Sullivan, J ;
Hawkins, N ;
Davy, E ;
Capparelli, C ;
Eli, A ;
Qian, YX ;
Kaufman, S ;
Sarosi, I ;
Shalhoub, V ;
Senaldi, G ;
Guo, J ;
Delaney, J ;
Boyle, WJ .
CELL, 1998, 93 (02) :165-176