促红细胞生成素对破骨细胞调控机理的研究

Erythropoietin receptor signaling pathways mediated osteoclast differentiation and activation

目的研究小鼠单核巨噬细胞在体外向破骨细胞分化的过程中,促红细胞生成素(erythropoietin,EPO)与破骨细胞表面受体Epor结合发挥作用的机理。方法 EPO作用于Epor受体沉默的经诱导的小鼠单核巨噬细胞,观察TRAP阳性多核细胞数目变化。Real-time PCR检测RAW264.7向破骨细胞分化过程中相关基因Epor、Nfatc1、Mmp9、EphrinB2基因的表达。结果与对照组比较,4天后,Epor沉默组的Nfatc1、EphrinB2 mRNA的表达明显升高(P<0.01),Ctsk Mmp9 mRNA的表达明显降低(P<0.01)。结论 EPO通过与破骨细胞表面受体Epor结合,引发破骨细胞内相关基因表达改变,进而影响破骨细胞的分化和活化。

Objective To investigate the mechanism of mediating osteoclast differentiation and activation by erythropoietin. Methods The mouse monocyte/macrophage cell line RAW264. 7 as an osteoclast precursor was treated with rhEpo and receptor activator of nuclear factor- κB （RANK） ligand （ RANKL）. The numbers of tartrate-resistant acid phosphatase （TRAP） staining positive and muhinucleated cells were counted after 5-9 days. The levels of Epor, Nfatcl, efnb2, matrix metalloproteinase-9 （Mmp-9） and cathepsin K （Ctsk） were examined by semi-quantitative real-time PCR. Results Compared with the control, the expression of Nfatcl, EphrinB2 mRNA was up-regulated （ P 〈 0. 01 ）, and the expression of Ctsk Mmp9 mRNA down-regulated （ P 〈 0.01 ） after four days. Conclusion Eythropoietin combined with osteoclast cell surface receptor Epor, initiated steoclast related gene expression changes, thereby influencing differentiation and activation of osteoclasts.