ATRA与BMP9对人骨肉瘤细胞增殖和成骨分化的影响及可能机制研究

发布时间：2018-07-17 07:08

【摘要】：骨肉瘤(Osteosarcoma,OS)是最常见的骨组织原发恶性肿瘤,并被认为是一种分化缺陷性疾病。虽然骨形态蛋白9(Bone morphogenetic protein 9,BMP9)对间充质干细胞而言,是最强的成骨诱导因子,但其并不能诱导骨肉瘤细胞的成骨分化。这可能是骨肉瘤的发病机制之一。全反式维甲酸(All-trans-retinoic acid,ATRA)能够成功诱导骨肉瘤细胞成骨分化;并且在脂肪前体细胞中,ATRA能增强BMP9所诱导的成骨分化作用。但是ATRA与BMP9在骨肉瘤细胞中是否具有同样的作用,尚还不明确。因此,在本文中,我们主要探讨这一点。本研究结果表明:在体外试验中,BMP9能够明显促进骨肉瘤143B细胞的增殖(p0.01),但并不能诱导其成骨分化;ATRA能够抑制143B细胞的增殖,并能成功诱导其成骨分化;且ATRA能够上调143B细胞中内源性BMP9的表达水平;过表达BMP9能够增强ATRA对143B细胞增殖及成骨分化的影响;ATRA能够明显增强磷酸化p38 MAPK(p-p38)的表达水平,而单独的BMP9却不能;但当BMP9与ATRA联用时,过表达BMP9能够增强ATRA对p-p38表达水平的影响;当ATRA存在时,BMP9对骨肉瘤143B细胞的抗增殖和成骨诱导作用均能够被p38 MAPK抑制剂(SB203580)所减弱(p0.01)。综上所述,本研究表明,BMP9对骨肉瘤143B细胞的成骨诱导作用能够被ATRA恢复,并且二者联合的抗增殖作用相比单用ATRA更明显,而这些均可能与激活p38MAPK信号通路相关。
[Abstract]:Osteosarcoma (Osteosarcoma OS) is the most common primary malignant tumor of bone tissue and is considered to be a kind of differentiation defect disease. Although bone morphogenetic protein 9 (BMP9) is the strongest osteogenic factor for mesenchymal stem cells, it can not induce osteogenic differentiation of osteosarcoma cells. This may be one of the pathogenesis of osteosarcoma. All trans retinoic acid (All-trans-retinoic) can successfully induce osteogenic differentiation of osteosarcoma cells and enhance the osteogenic differentiation induced by BMP9 in adipose precursor cells. But it is unclear whether ATRA and BMP9 have the same effect in osteosarcoma cells. Therefore, in this article, we mainly discuss this point. The results showed that BMP9 could significantly promote the proliferation of osteosarcoma 143B cells in vitro (p0.01), but it could not induce osteogenic differentiation. ATRA could inhibit the proliferation of 143B cells and induce its osteogenic differentiation successfully. ATRA could up-regulate the expression of endogenous BMP9 in 143B cells, and overexpression of BMP9 could enhance the proliferation and osteogenic differentiation of 143B cells. ATRA could significantly enhance the expression of phosphorylated p38 MAPK (p-p38), but BMP9 alone could not. When combined with BMP9 and ATRA, overexpression of BMP9 could enhance the effect of BMP9 on the expression of p-p38, and the anti-proliferation and osteogenic induction of BMP9 on osteosarcoma 143B cells could be weakened by p38 MAPK inhibitor (SB203580) (p0.01). To sum up, the osteogenesis induced by BMP9 on osteosarcoma 143B cells can be recovered by ATRA, and the anti-proliferation effect of BMP9 is more obvious than that of ATRA alone, which may be related to the activation of p38 MAPK signaling pathway.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R738.1

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