Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a newly discovered adipokine that widely participates in diabetes mellitus, polycystic ovarian syndrome and other disorders of metabolism. However, the effect of vaspin on the regulation of osteogenesis and the mechanism responsible are still unclear. Here, we found that vaspin can attenuate the osteogenic differentiation of the preosteoblast cell line MC3T3-E1 in a dose-dependent way; also, during this process, the expression of miRNA-34c (miR-34c) was significantly increased. Down-regulation of the expression of miR-34c in MC3T3-E1 diminished the osteogenic inhibitory effect of vaspin, while the up-regulation of miR-34c increased this effect through its target gene Runx2. Meanwhile, we found that vaspin could also activate the PI3K-Akt signalling pathway. Blocking the PI3K-Akt signalling pathway with specific inhibitors could decrease the osteogenic inhibitory effect of vaspin as well as the expression level of miR-34c. Furthermore, knock-down of miR-34c could promote the activation of Akt, which was probably realised by targeting c-met expression. Thus, PI3K-Akt and miR-34c constituted a modulation loop and controlled the expression of each other. Taken together, our study showed that vaspin could inhibit the osteogenic differentiation in vitro, and the PI3K-Akt/miR-34c loop might be the underlying mechanism.
Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a newly discovered adipokine that widely participates in diabetes mellitus, polycystic ovarian syndrome and other disorders of metabolism. However, the effect of vaspin on the regulation of osteogenesis and the mechanism responsible are still unclear. Here, we found that vaspin can attenuate the osteogenic differentiation of the preosteoblast cell line MC3T3-E1 in a dose-dependent way; also, during this process, the expression of miRNA-34c (miR-34c) was significantly increased. Down-regulation of the expression of miR-34c in MC3T3-E1 diminished the osteogenic inhibitory effect of vaspin, while the up-regulation of miR-34c increased this effect through its target gene Runx2. Meanwhile, we found that vaspin could also activate the PI3K-Akt signalling pathway. Blocking the PI3K-Akt signalling pathway with specific inhibitors could decrease the osteogenic inhibitory effect of vaspin as well as the expression level of miR-34c. Furthermore, knock-down of miR-34c could promote the activation of Akt, which was probably realised by targeting c-met expression. Thus, PI3K-Akt and miR-34c constituted a modulation loop and controlled the expression of each other. Taken together, our study showed that vaspin could inhibit the osteogenic differentiation in vitro, and the PI3K-Akt/miR-34c loop might be the underlying mechanism.Fat is the largest endocrine organ in the human body and has a complex connection with bone. In the past, it was widely accepted that fat was a protective factor for bone mass. The loading effect caused by fat mass cooperates with that of muscle mass and can protect the bone mineral density (BMD) from declining 1 . However, recent studies have challenged the conventional standpoint which states that fat might be a beneficial factor for bone health. One study carried out in 197 elderly patients showed that fracture risk was positively related to the fat mass in the bone marrow 2 , and this viewpoint gained support from additional researches. According to these studies, negative associations between fat mass and bone tissue have been demonstrated in children, men, and pre-and post-menopausal women [3][4][5][6][7][8][9] . Recently, visceral adipose tissue (VAT) has gained increasing attention on the basis of robust evidence linking VAT and insulin resistance, metabolic syndrome, dyslipidaemia, cardiovascular disease, hypertension, and cancer [10][11][12][13][14] . In addition, according to Cohen's study, VAT has been shown to show the most significant association with lower BMD; post-menopausal women with more VAT showed a significant decline in both BMD and microarchitecture, and also the bone regeneration rate was greatly suppressed 15 . Furthermore, the similar result was found in Júnior's study, who found that BMD was negatively correlated with VAT 16. These results all indicated that VAT might have a negative effect on bone, and the adipokines might be responsible.To date, many adipokines have been found to participate in bone metabol...
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