人甲状旁腺激素（1-34）在人成骨肉瘤细胞中对基质Gla蛋白及Wnt/β-catenin信号通路的调节作用 postprint

Abstract: Objective To observe the effect of parathyroid hormone (PTH)(1-34) on the expression of matrix Gla protein (MGP) and Wnt/β-catenin signaling pathway and elucidate the possible molecular mechanism of PTH (1-34) in the prevention and treatment of osteoporosis. Methods MG63 cells treated with PTH (1-34) at 10-9, 10-8, and 10-7 mol/L, alone or in combination with Wnt/beta-catenin signaling pathway inhibitors DKK-1 (200 ng/ml) were examined for mRNA and protein expressions related with Wnt/β-catenin signaling with real-time PCR and Western blotting. The cell differentiation after the treatment was assessed with alkaline phosphatase (ALP) staining and cell viability assay. Results PTH (1-34) significantly increased the expression of MGP in a dose-dependent manner in MG63 cells (P<0.05 or P<0.01). PTH treatment obviously enhanced ALP activity in the cells, and this effect was suppressed by DKK-1. Combined treatment with DKK-1 partially blocked PTH-induced enhancement of ALP activity (P<0.05). PTH promoted the expression of MGP and enhanced LRP5, β-catenin, and Runx2 expressions in Wnt/β-catenin signaling pathway at both protein and mRNA levels (P<0.05 or P<0.01). DKK-1 partially blocked the effect of PTH (1-34) on Wnt/β-catenin signaling pathway (P<0.05) without affecting MGP expression. Conclusion PTH (1-34) significantly increases the expressions of MGP and proteins in the Wnt/β-catenin signaling pathway. Wnt/β-catenin signaling pathway and MGP mediate the regulation of osteogenosis by PTH.