凝血酶和PAR-1受体对成骨细胞白介素-6和成纤维细胞生长因子-2表达的影响

目的 探讨凝血酶对小鼠成骨细胞某些因子表达的调节作用.方法 使用小鼠颅骨的成骨细胞,通过荧光定量PCR方法 和人工合成的PAR-1或PAR-4特异性激活短肽了解受体介导的凝血酶对成骨细胞因子表达的影响.结果 凝血酶不影响成骨细胞转化生长因子、血小板生长因子A、胰岛素样生长因子-Ⅰ和-Ⅱ的表达,凝血酶和PAR-1 受体激活肽可以显著上调成骨细胞成纤维细胞生长因子-2 (FGF-2) 和白介素-6 (IL-6) 的表达,但对IL-6表达的调节作用,凝血酶远较PAR-1激活肽为强,而PAR-4特异性激活肽并不影响这两种因子的表达.结论 凝血酶可以促进小鼠成骨细胞FGF-2 和IL-6的表达,此作用可能是通过PAR-1和非PAR-1通路介导的,凝血酶对FGF-2表达的调节可能完全是由PAR-1 介导的,而凝血酶对IL-6表达的影响部分是由PAR-1 介导的,部分可能是由未知受体介导的.PAR-4并不参与介导凝血酶对FGF-2和IL-6 表达的调节作用.

The regulation effects of thrombin on mouse osteoblast FGF-2 and IL-6 expression

Objective The aim of this study is to investigate the regulation effects of thrombin on the expression of some factors expressed in osteoblasts. Methods The regulation effects on mRNA expression of some selected osteoblast-derived factors by thrombin and synthetic peptides that specifically activate PAR-1 and PAR-4 were investigated by quantitative real time PCR in mouse primary osteoblasts. Results The expression of IGF-Ⅰ, IGF-Ⅱ and PDGFA was not affected by the application of thrombin. Thrombin stimulated the mRNA expression of interleukine-6 and fibroblast growth factor-2. The PAR-1-activating peptide can promote the expression of FGF-2 and interleukine-6. The effect of thrombin on the regulation of IL-6 expression was much more potential than that of PAR-1AP. However, in the regulation of FGF-2 expression the effects of thrombin was similar to PAR-1AP. PAR-4-activating peptide was no effect on the regulation of either IL-6 or FGF-2 expression. Conclusion The results presented here demonstrate that thrombin up-regulates mRNA expression of IL-6 and FGF-2 through PAR-1-dependent and independent pathways. Thrombin regulated the expression of FGF2 is fully PAR-1-dependent. Thrombin up-regulated the expression of IL-6 was partially PAR-1-dependent in mouse osteoblast. PAR-4 does not participate this activity.