Connective tissue growth factor is a downstream mediator for preptin-induced proliferation and differentiation in human osteoblasts
Connective tissue growth factor is a downstream mediator for preptin-induced proliferation and differentiation in human osteoblasts
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结缔组织生长因子是 preptin 诱导的人成骨细胞增殖和分化的下游介质
DOI：
10.1007/s00726-009-0281-4
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发表时间：
2010-03-01
期刊：
影响因子：
3.5
通讯作者：
Liao, Er-Yuan
中科院分区：
文献类型：
--
作者：
Liu, You-Shuo;Lu, Ying;Liao, Er-Yuan
Preptin是一种新分离的34个氨基酸的肽激素，与胰岛素和胰胰素共同分泌，已成为骨代谢的调节元件，但其机制尚不清楚。我们评估了preptin对人成骨细胞增殖和分化的影响，并探讨了其机制。我们的研究结果表明，preptin促进人成骨细胞增殖和碱性磷酸酶活性。通过小干扰RNA （siRNA）抑制preptin以剂量和时间依赖性方式上调的结缔组织生长因子（CTGF），可消除preptin诱导的人成骨细胞的增殖和分化。在人成骨细胞中，Preptin诱导ERK有丝分裂原活化蛋白激酶（MAPK）活化，但不诱导p38或JNK活化。此外，ERK抑制剂PD98059预处理人成骨细胞，可消除preptin诱导的CTGF分泌，阻断preptin对成骨细胞增殖分化的促进作用。这些数据表明，preptin参与了人成骨细胞中ERK/CTGF介导的骨合成代谢，并可能有助于在高胰岛素状态（如肥胖）下观察到的骨量保存。
Preptin, a newly isolated 34-amino-acid peptide hormone that is cosecreted with insulin and amylin from pancreatic beta-cells, has emerged as a regulatory element in bone metabolism, but its mechanism remains unclear. We assessed the effects of preptin on proliferation and differentiation of human osteoblasts and investigated the mechanism involved. Our results demonstrated that preptin promoted human osteoblasts proliferation and alkaline phosphatase activity. Suppression of connective tissue growth factor (CTGF), which was upregulated by preptin in a dose- and time-dependent manner, with small interfering RNA (siRNA) abolished the preptin-induced human osteoblasts proliferation and differentiation. Preptin induced activation of ERK mitogen-activated protein kinase (MAPK), but not p38 or JNK in human osteoblasts. Furthermore, pretreatment of human osteoblasts with the ERK inhibitor PD98059 abolished the preptin-induced CTGF secretion and blocked the promoting effect of preptin on osteoblasts proliferation and differentiation. These data demonstrated that preptin is involved in bone anabolism mediated by ERK/CTGF in human osteoblasts and may contribute to the preservation of bone mass observed in hyperinsulinemic states, such as obesity.