Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Orthopedics, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, P.R. China.
Int J Mol Med. 2018 Sep;42(3):1247-1256. doi: 10.3892/ijmm.2018.3716. Epub 2018 Jun 5.
Cartilage‑derived morphogenetic protein‑1 (CDMP1) is a polypeptide growth factor with specific cartilage inducibility, which is predominantly expressed in the developmental long bone cartilage core and in the pre‑cartilage matrix in the embryonic stage. The aim of the present study was to investigate the roles and the mechanisms of CDMP1 overexpression on the apoptosis of rat dorsal root ganglia (DRG) neurons that were induced by inflammatory cytokines. Cell counting Kit‑8 assay, flow cytometry and TdT‑mediated dUTP nick‑end labeling assay were performed to examine cell viability and apoptosis. ELISA, hematoxylin and eosin staining and immunohistochemistry assays were performed to examine the levels of several factors in DRG tissues. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction assays were used to determine the mRNA and protein expression levels, respectively. The results demonstrated that CDMP1 expression was downregulated, while inflammatory cytokine expression was upregulated in DRG tissues derived from lumbar disc herniation (LDH) model rats. In addition, DRG cells from LDH rats exhibited increased apoptosis compared with control rats. CDMP1 overexpression enhanced the cell viability of inflammatory cytokine‑induced DRG cells, and suppressed the apoptosis of inflammatory cytokine‑induced DRG cells via regulating the expression levels of Caspase‑3/8/9, BCL2 apoptosis regulator, and BCL2 associated X. Furthermore, CDMP1 overexpression was demonstrated to affect the Wnt/β‑Catenin pathway in the inflammatory cytokine‑induced DRG cells. In conclusion, the present findings suggested that CDMP1 overexpression mediated inflammatory cytokine‑induced apoptosis via Wnt/β‑Catenin signaling in rat DRG cells.
软骨衍生形态发生蛋白 1（CDMP1）是一种具有特定软骨诱导性的多肽生长因子，主要在发育中的长骨软骨核心和胚胎期的软骨前基质中表达。本研究旨在探讨 CDMP1 过表达对炎性细胞因子诱导的大鼠背根神经节（DRG）神经元凋亡的作用及其机制。通过细胞计数试剂盒-8 检测、流式细胞术和 TdT 介导的 dUTP 缺口末端标记检测来检测细胞活力和凋亡。通过 ELISA、苏木精和伊红染色和免疫组织化学检测来检测 DRG 组织中几种因子的水平。通过 Western blot 分析和逆转录-定量聚合酶链反应检测分别来确定 mRNA 和蛋白表达水平。结果表明，腰椎间盘突出症（LDH）模型大鼠的 DRG 组织中 CDMP1 表达下调，而炎性细胞因子表达上调。此外，与对照组大鼠相比，LDH 大鼠的 DRG 细胞凋亡增加。CDMP1 过表达增强了炎性细胞因子诱导的 DRG 细胞的活力，并通过调节 Caspase-3/8/9、BCL2 凋亡调节因子和 BCL2 相关 X 的表达水平，抑制了炎性细胞因子诱导的 DRG 细胞的凋亡。此外，还发现 CDMP1 过表达影响了炎性细胞因子诱导的 DRG 细胞中的 Wnt/β-连环蛋白通路。综上所述，本研究结果表明，CDMP1 过表达通过 Wnt/β-连环蛋白信号通路介导炎性细胞因子诱导的大鼠 DRG 细胞凋亡。
