Department of Anesthesia Surgery, Jining NO. 1 People's Hospital, Affiliated Jining NO. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining 272000, Shandong, China.
Department of Emergency Trauma Surgery, Jining NO. 1 People's Hospital, Affiliated Jining NO. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining 272000, Shandong, China.
Biosci Rep. 2019 Mar 28;39(3). doi: 10.1042/BSR20182462. Print 2019 Mar 29.
Mechanical overload is a risk factor of disc degeneration. It can induce disc degeneration through mediating cell apoptosis. Mechano growth factor (MGF) has been reported to inhibit mechanical overload-induced apoptosis of chondrocytes. The present study is aimed to investigate whether MGF can attenuate mechanical overload-induced nucleus pulposus (NP) cell apoptosis and the possible signaling transduction pathway. Rat NP cells were cultured and subjected to mechanical overload for 7 days. The control NP cells did not experience mechanical load. The exogenous MGF peptide was added into the culture medium to investigate its protective effects. NP cell apoptosis ratio, caspase-3 activity, gene expression of Bcl-2, Bax and caspase-3, protein expression of cleaved caspase-3, cleaved PARP, Bax and Bcl-2 were analyzed to evaluate NP cell apoptosis. In addition, activity of the p38 MAPK pathway was also detected. Compared with the control NP cells, mechanical overload significantly increased NP cell apoptosis and caspase-3 activity, up-regulated gene/protein expression of pro-apoptosis molecules (i.e. Bax, caspase-3, cleaved caspase-3 and cleaved PARP) whereas down-regulated gene/protein expression of anti-apoptosis molecule (i.e. Bcl-2). However, exogenous MGF partly reversed these effects of mechanical overload on NP cell apoptosis. Further results showed that activity of the p38 MAPK pathway of NP cells cultured under mechanical overload was decreased by addition of MGF peptide. In conclusion, MGF is able to attenuate mechanical overload-induced NP cell apoptosis, and the p38 MAPK signaling pathway may be involved in this process. The present study provides that MGF supplementation may be a promising strategy to retard mechanical overload-induced disc degeneration.
机械性超负荷是椎间盘退变的一个危险因素。它可以通过介导细胞凋亡来诱导椎间盘退变。已经有报道称机械生长因子（MGF）可以抑制软骨细胞的机械性超负荷诱导的细胞凋亡。本研究旨在探讨 MGF 是否可以减轻机械性超负荷诱导的髓核（NP）细胞凋亡及其可能的信号转导途径。原代大鼠 NP 细胞培养并进行机械性超负荷 7 天。对照组 NP 细胞不经历机械负荷。向培养液中加入外源性 MGF 肽以研究其保护作用。分析 NP 细胞凋亡率、半胱天冬酶-3 活性、Bcl-2、Bax 和半胱天冬酶-3 基因表达、cleaved caspase-3、cleaved PARP、Bax 和 Bcl-2 蛋白表达，以评估 NP 细胞凋亡。此外，还检测了 p38 MAPK 通路的活性。与对照组 NP 细胞相比，机械性超负荷显著增加了 NP 细胞凋亡和半胱天冬酶-3 活性，上调了促凋亡分子（即 Bax、caspase-3、cleaved caspase-3 和 cleaved PARP）的基因/蛋白表达，而下调了抗凋亡分子（即 Bcl-2）的基因/蛋白表达。然而，外源性 MGF 部分逆转了机械性超负荷对 NP 细胞凋亡的这些作用。进一步的结果表明，加入 MGF 肽后，机械性超负荷培养的 NP 细胞中 p38 MAPK 通路的活性降低。总之，MGF 能够减轻机械性超负荷诱导的 NP 细胞凋亡，p38 MAPK 信号通路可能参与了这一过程。本研究提供了补充 MGF 可能是一种延缓机械性超负荷诱导的椎间盘退变的有前途的策略。
