| RRC ID |
42392
|
| 著者 |
Kim SW, Her SJ, Park SJ, Kim D, Park KS, Lee HK, Han BH, Kim MS, Shin CS, Kim SY.
|
| タイトル |
Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells.
|
| ジャーナル |
Bone
|
| Abstract |
Ghrelin is a 28-amino-acid peptide identified in the stomach as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates the release of growth hormone at the hypothalamus and pituitary level. Although GHS-Rs are expressed in a variety of peripheral tissues, little is known about its effect on bone independent of GH/IGF-1 axis. This study was undertaken to investigate whether ghrelin exerts a direct effect on osteoblasts. We identified mRNA and protein expression of GHS-R in primary osteoblasts as well as a number of osteoblastic cell lines, including MC3T3-E1, ROS 17/2.8, UMR-106, MG63, and SaOS2 cells. Treatment of ghrelin (10(-11) to 10(-7) M) to MC3T3-E1 cells showed dose-dependent stimulation of proliferation, which was abrogated by treatment with [d-Lys]-GHRP-6 (10(-3) M), a selective antagonist of the ghrelin receptor. Ghrelin activated ERK1/2 MAPK and pretreatment with MAPK kinase inhibitors, PD98059 attenuated the ghrelin-induced cell proliferation. Ghrelin also inhibited TNFalpha-induced apoptosis and suppressed caspase-3 activation that occurs in response to TNFalpha as well as during in vitro differentiation process. Moreover, ghrelin treatment enhanced in vitro osteoblast differentiation as evidenced by matrix mineralization, alkaline phosphatase activity, and osteoblast-specific gene expression. These results suggest that ghrelin promotes proliferation and differentiation and inhibits apoptosis of osteoblasts.
|
| 巻・号 |
37(3)
|
| ページ |
359-69
|
| 公開日 |
2005-9-1
|
| DOI |
10.1016/j.bone.2005.04.020
|
| PII |
S8756-3282(05)00180-8
|
| PMID |
15978880
|
| MeSH |
Animals
Apoptosis / drug effects*
Cell Differentiation / drug effects*
Cell Line
Cell Proliferation / drug effects
Gene Expression Regulation / genetics
Ghrelin
MAP Kinase Signaling System / drug effects
Mice
Mitogen-Activated Protein Kinases / metabolism
Osteoblasts / cytology*
Osteoblasts / drug effects*
Peptide Hormones / pharmacology*
Rats
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism
Receptors, Ghrelin
Tumor Necrosis Factor-alpha / pharmacology
|
| IF |
4.147
|
| 引用数 |
148
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
