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首页> 外文期刊>Journal of orthopaedic research >PTHrP increases RANKL expression by stromal cells from giant cell tumor of bone
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PTHrP increases RANKL expression by stromal cells from giant cell tumor of bone

机译:PTHrP通过骨巨细胞瘤的基质细胞增加RANKL表达

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摘要

Giant cell tumor of bone (GCT) presents with numerous osteoclast-like multinucleated giant cells that are principally responsible for the extensive bone resorption by the tumor. Although the precise etiology of GCT remains uncertain, the accumulation of giant cells is partially due to the high expression of the receptor activator of nuclear factor-kB ligand (RANKL) from the neoplastic stromal cells. Here, we have investigated whether parathyroid hormone-related protein (PTHrP) plays a role in the pathogenesis of GCT. Immunohistochemistry results revealed PTHrP expression in the stromal cells of the tumor, and that its receptor, the parathyroid hormone type 1 receptor (PTH1R), is expressed by both the stromal cells and giant cells. PCR and Western blot analyses confirmed the expression of PTHrP and PTH1R by isolated stromal cells from five patients presenting with GCT. Treatment of GCT stromal cells with varying concentrations of PTHrP (1-34) significantly increased both RANKL gene expression and the number of multinucleated cells formed from RAW 264.7 cells in co-culture experiments, whereas inhibition of PTHrP with a neutralizing antibody decreased RANKL gene expression. These results suggest that PTHrP is expressed within GCT by the stromal cells and can contribute to the abundant RANKL expression and giant cell formation within the tumor.
机译:骨巨细胞瘤(GCT)呈现出大量破骨细胞样多核巨细胞,这些巨细胞主要负责肿瘤的广泛骨吸收。尽管GCT的确切病因仍不确定,但巨细胞的积累部分归因于肿瘤基质细胞中核因子-kB配体(RANKL)受体激活剂的高表达。在这里,我们调查了甲状旁腺激素相关蛋白(PTHrP)是否在GCT的发病机理中起作用。免疫组织化学结果显示PTHrP在肿瘤基质细胞中表达,其受体甲状旁腺激素1型受体(PTH1R)由基质细胞和巨细胞表达。 PCR和Western blot分析证实了来自5例GCT患者的分离的基质细胞中PTHrP和PTH1R的表达。在共培养实验中,用不同浓度的PTHrP(1-34)处理GCT基质细胞可显着提高RANKL基因表达和由RAW 264.7细胞形成的多核细胞数量,而用中和抗体抑制PTHrP可降低RANKL基因表达。这些结果表明,PTHrP在GCT中由间质细胞表达,可以促进肿瘤内大量RANKL表达和巨细胞形成。

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