Synergistic Effect of Combined Growth Factors in Porcine Intervertebral Disc Degeneration
Synergistic Effect of Combined Growth Factors in Porcine Intervertebral Disc Degeneration
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DOI：
10.3109/03008207.2013.775258
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Kim, Song-Ja
中科院分区：
文献类型：
--
作者：
Cho, Hongsik;Lee, Sangmin;Kim, Song-Ja
尽管椎间盘退变是最常见的致病原因之一，但其病因尚不清楚。在健康的椎间盘中，由于生长因子和分解代谢细胞因子的复杂调控，细胞外基质(ECM)的合成和分解速度是平衡的。在这些生理性生长因子中，重要的是转化生长因子-β1和骨形态发生蛋白-2。椎间盘退变被认为与蛋白多糖(PG)合成和细胞因子诱导的降解之间的动态平衡的丧失有关，导致基质金属蛋白酶(MMP)家族的上调和细胞外基质产生的下调。已经尝试了几种使用生物制剂的策略来管理IVD退变，改善IVD细胞的功能和合成代谢能力，并抑制基质降解。本研究的目的是比较合成代谢细胞因子BMP-2和转化生长因子-β1与分解代谢细胞因子白介素1-β和肿瘤坏死因子-α对猪纤维环(AF)的影响。这项研究的结果表明，在正常纤维环细胞中应用促炎细胞因子如肿瘤坏死因子-α和白介素1-β，可显著增加组织中降解性蛋白水解酶-1的水平。联合使用最小剂量的BMP-2和转化生长因子-β1可导致基质金属蛋白酶-1的降低和聚集素的增加，这比单独使用任何一种细胞因子都要大，这表明联合细胞因子的协同作用。
Although intervertebral disc (IVD) degeneration is one of most common causes of morbidity, its etiology remains unclear. In healthy discs, the rates of synthesis and breakdown of the extracelluar matrix (ECM) are in equilibrium because of intricate regulation by growth factors and catabolic cytokines. Important among these physiologic growth factors are transforming growth factor-beta (TGF-beta 1) and bone morphogenetic protein-2 (BMP-2). Disc degeneration is thought to be associated with a loss of this homeostasis between proteoglycan (PG) synthesis and cytokine-induced degradation leading to up-regulation of matrix metalloproteinases (MMP) families and down-regulation of extracelluar matrix production. Several strategies using biological agents have been attempted to manage IVD degeneration, improving the function and anabolic capabilities of IVD cells and inhibiting matrix degradation. The purpose of this study is to compare the effects of the anabolic cytokines BMP-2 and TGF-beta 1 with those of the catabolic cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) on porcine annulus fibrosus (AF). The results of this study show that the application of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-1 beta to normal annulus fibrosus cells leads to a significant increase in tissue levels of the degradative protease MMP-1. Treatment with a combination of minimum doses of both BMP-2 and TGF-beta 1 caused a greater decrease in MMP-1 and increase in aggrecan than either cytokine alone, suggesting a synergistic effect of the combined cytokines.