Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells.
Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells.
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DOI：
10.1186/1471-2121-8-51
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发表时间：
2007-11-29
期刊：
影响因子：
--
通讯作者：
Sugimoto T
中科院分区：
文献类型：
--
作者：
Kanazawa I;Yamaguchi T;Yano S;Yamauchi M;Yamamoto M;Sugimoto T
脂联素是内脏脂肪堆积引起的代谢综合征的关键介质。已知脂联素及其受体在成骨细胞中表达，但它们在骨代谢中的作用尚不清楚。在本研究中，我们研究了脂联素对成骨细胞MC3T3-E1增殖、分化和矿化的影响。RT-PCR检测细胞中脂联素受体1型(AdipoR1mRNA)的表达。脂联素和药物激活剂5-氨基咪唑-4-甲酰胺核苷(AICAR)均可使细胞内的腺苷一磷酸活化蛋白激酶(AMP)磷酸化。AdipoR1小干扰RNA(SiRNA)能有效地抑制受体基因的表达，这种抑制作用可持续10天之久。实时荧光定量聚合酶链式反应检测到I型胶原和骨钙素mRNA的表达降低，von Kossa和茜素红染色检测到碱性磷酸酶活性和矿化能力降低。相反，在野生型MC3T3-E1细胞中，AICAR(0.01-0.5 mM)对AMP激酶的激活促进了细胞的增殖、分化和矿化。BrdU比色法显示，加入脂联素(0.0 1~1.0μg/ml)也能促进其增殖。Osterix，而不是RUNX-2，似乎参与了这些过程，因为AdipoR1 siRNA转染和AICAR处理分别抑制和增强了Osterix mRNA的表达。综上所述，本研究提示脂联素通过自分泌和/或旁分泌方式通过AdipoR1和AMP激酶信号通路刺激成骨细胞的增殖、分化和矿化。
Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively. Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions.
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影响因子：
8.2
作者：
Kefas, BA;Heimberg, H;Casteele, M
通讯作者：
Casteele, M
DOI：
10.1083/jcb.200610046
发表时间：
2007-02-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
通讯作者：
Franceschi RT
影响因子：
5.8
作者：
GLAUBER, HS;VOLLMER, WM;ORWOLL, ES
通讯作者：
ORWOLL, ES
影响因子：
56.9
作者：
Mundy, G;Garrett, R;Gutierrez, G
通讯作者：
Gutierrez, G
影响因子：
64.8
作者：
Minokoshi, Y;Kim, YB;Kahn, BB
通讯作者：
Kahn, BB