Synergistic Effect of Combined Growth Factors in Porcine Intervertebral Disc Degeneration

被引:84
作者
Cho, Hongsik [1 ,2 ,3 ]
Lee, Sangmin [1 ]
Park, Sang-Hyug [4 ]
Huang, Jinsong [1 ]
Hasty, Karen A. [1 ,2 ,3 ]
Kim, Song-Ja [5 ]
机构
[1] Univ Tennessee, Ctr Hlth Sci, Dept Orthopaed Surg & Biomed Engn, Memphis, TN 38163 USA
[2] Campbell Clin, Dept Orthopaed Surg, Memphis, TN USA
[3] Vet Affairs Med Ctr, Memphis, TN USA
[4] Jungwon Univ, Dept Biomed Engn, Chungbuk, South Korea
[5] Kongju Natl Univ, Dept Biol Sci, Kong Ju 314701, South Korea
基金
新加坡国家研究基金会;
关键词
annulus fibrosus (AF); intervertebral disc (IVD); matrix metalloproteinase (MMP); interleukin-1 beta (IL-1 beta); tumor necrosis factor-alpha (TNF-alpha); bone morphogenetic protein (BMP); transforming growth factor-beta (TGF-beta); MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; NUCLEUS PULPOSUS; GENE-THERAPY; EXPRESSION; CELLS; CYTOKINES; STIMULATION; RECEPTORS; ALPHA;
D O I
10.3109/03008207.2013.775258
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:181 / 186
页数:6
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