Synergistic Effect of Nerve Growth Factor and Insulin-Like Growth Factor-1 on Providing a Pro-Survival, Anti-Apoptotic Benefit and Increased Extracellular Matrix Synthesis in Stressed Rat Intervertebral Disc Cells

摘要

Objective: The purpose of the study was to investigate the effect of nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) in preventing apoptosis and increasing extracellular matrix synthesis in serum deprived rat disc cells.Methods: Expression of tropomyosin-related kinase A (TrkA) receptor and IGF-1 receptor (IGF-1R) was examined in rat annulus fibrosus (AF) cells. We identified and quantified the degree of expression of TrkA and IGF-1R and apoptosis of the cells maintained in either 10% (normal control) or 0% (apoptosis-promoting condition) fetal bovine serum (FBS). We analyzed the effect of NGF (100 ng/ml) and IGF-1 (500 ng/ml) in preventing apoptosis and increasing synthesis of extracellular matrix proteins in the cells maintained in 0% FBS.Results: Expression of TrkA and IGF-1R was detectable in rat AF cells and the degree of expression of TrkA and IGF-1R decreased in the cells treated with 0% FBS but some expression was still detectable. Apoptosis of the cells significantly increased when maintained in 0% FBS. Despite 0% FBS condition, each application of NGF and IGF-1 reduced apoptosis of the cells by 2% and 5% with a subsequent increase in synthesis of aggrecan, collagen-1 and -2. The combined application of NGF and IGF-1 more significantly decreased apoptosis of the cells by 9% and increased synthesis of aggrecan, collagen-1 and -2 in the cells.Conclusions: Our result suggests that NGF and IGF-1 may play a therapeutic role in slowing disc degeneration, which is due to an inappropriate or excessive apoptosis of the disc cells.