Abstract
BackgroundAdiponectin 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.ResultsAdiponectin 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.ConclusionTaken 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.
Highlights
Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation
By using reverse transcription (RT)-polymerase chain reaction (PCR), we confirmed that Adiponectin receptor type 1 (AdipoR1) mRNA, but not AdipoR2, was expressed in MC3T3-E1 cells (Fig. 1A)
SiRNA-AdipoR1 blocked the expression of AdipoR1 mRNA (Fig. 1B), while a treatment with cyclophilin B (CypB) small interfering RNA (siRNA) blocked the expression of CypB mRNA (Fig. 1C), showing that the knockdown effect of siRNA-AdipoR1 was specific
Summary
Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin is one of the adipocytokines and highly expressed in adipose tissue. It is abundantly present in plasma [8] and has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity [9,10,11]. Several studies indicate that AdipoR1 and AdipoR2 serve as receptors for globular and full-length adiponectin, respectively, and that their stimulation by adiponectin results in increased AMP-activated protein kinase (AMP kinase) and PPARα ligand activities as well as fatty acid oxidation and glucose uptake in the liver and skeletal muscle [12,13,14]. Obesity decreases AdipoR expression levels, thereby reducing adiponectin sensitivity and enhancing insulin resistance [15]. Genetic variations in AdipoR have been reported to be linked to a common genetic predisposition to insulin resistance or type 2 diabetes mellitus [16]
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