Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, 410011 Hunan, People's Republic of China.
Amino Acids. 2010 Mar;38(3):763-9. doi: 10.1007/s00726-009-0281-4. Epub 2009 Mar 31.
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.
Preptin 是一种新分离的 34 个氨基酸的肽类激素，与胰岛素和胰岛淀粉样多肽一起从胰岛β细胞中共同分泌，已成为骨代谢的调节因子，但作用机制尚不清楚。我们评估了 Preptin 对人成骨细胞增殖和分化的影响，并探讨了相关机制。结果表明 Preptin 促进人成骨细胞增殖和碱性磷酸酶活性。用小干扰 RNA（siRNA）抑制结缔组织生长因子（CTGF）的表达，CTGF 可被 Preptin 剂量和时间依赖性地上调，从而消除了 Preptin 诱导的人成骨细胞增殖和分化。Preptin 诱导人成骨细胞 ERK 丝裂原活化蛋白激酶（MAPK）的激活，但不激活 p38 或 JNK。此外，用 ERK 抑制剂 PD98059 预处理人成骨细胞可消除 Preptin 诱导的 CTGF 分泌，并阻断 Preptin 对成骨细胞增殖和分化的促进作用。这些数据表明 Preptin 通过 ERK/CTGF 参与人成骨细胞的骨合成代谢，可能有助于肥胖等高胰岛素血症状态下骨量的维持。
