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T140 通过 SDF-1/CXC 受体-4 信号通路抑制大鼠椎间盘终板软骨细胞凋亡,促进增殖和基质形成。

T140 Inhibits Apoptosis and Promotes Proliferation and Matrix Formation Through the SDF-1/CXC Receptor-4 Signaling Pathway in Endplate Chondrocytes of the Rat Intervertebral Discs.

机构信息

Department of Rehabilitation, Yantai Yuhuangding Hospital, Yantai, China.

Department of Cardiology, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

World Neurosurg. 2020 Jan;133:e165-e172. doi: 10.1016/j.wneu.2019.08.140. Epub 2019 Aug 30.

DOI:10.1016/j.wneu.2019.08.140
PMID:31476465
Abstract

BACKGROUND

Cartilaginous endplate (CEP), a thin layer of hyaline cartilage located between the vertebral endplate and nucleus pulposus, transports the nutrient into the disc. The objective of this study was to evaluate the influence of T140 (polyphemusin II-derived peptide) on the CEP cell growth, apoptosis, and the matrix formation via the stromal cell-derived factor-1 (SDF-1)/cysteine X cysteine (CXC) receptor-4 (CXCR4) signaling pathway.

METHODS

Sprague-Dawley rats were euthanized by cervical dislocation and dissected for the isolation and the appraisal of CEP cells that were extracted from the endplate in rat intervertebral discs and were then added with different concentrations of reagents (SDF-1 and T140). The effect of T140 on CEP cell proliferation and apoptosis were analyzed. The messenger RNA (mRNA) and protein expressions of CXCR4, prominin-1, proteoglycans, type II collagen, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis.

RESULTS

T140 promoted the proliferation of CEP cells and inhibited the apoptosis of CEP cells. Additionally, T140 suppressed the mRNA and protein expression of CXCR4, prominin-1, and Bcl-2 associated X protein, and increased the mRNA and protein expression of proteoglycans, type II collagen, and Bcl-2.

CONCLUSIONS

T140 promotes the proliferation and matrix formation and inhibits the apoptosis of CEP cells by blocking the SDF-1/CXCR4 signaling pathway in vitro, which provides a certain therapeutic effect on the degeneration of intervertebral discs.

摘要

背景

软骨终板(CEP)是位于椎体终板和髓核之间的一层薄的透明软骨,将营养物质输送到椎间盘内。本研究旨在评估 T140(多瘤蛋白 II 衍生肽)通过基质细胞衍生因子-1(SDF-1)/CXC 趋化因子受体-4(CXCR4)信号通路对 CEP 细胞生长、凋亡和基质形成的影响。

方法

通过颈椎脱位处死 Sprague-Dawley 大鼠,解剖分离大鼠椎间盘终板中的 CEP 细胞,并加入不同浓度的试剂(SDF-1 和 T140)。分析 T140 对 CEP 细胞增殖和凋亡的影响。通过逆转录定量聚合酶链反应和 Western blot 分析分析 CXCR4、Prominin-1、糖胺聚糖、II 型胶原、B 细胞淋巴瘤-2(Bcl-2)和 Bcl-2 相关 X 蛋白的信使 RNA(mRNA)和蛋白表达。

结果

T140 促进 CEP 细胞增殖,抑制 CEP 细胞凋亡。此外,T140 抑制 CXCR4、Prominin-1 和 Bcl-2 相关 X 蛋白的 mRNA 和蛋白表达,增加糖胺聚糖、II 型胶原和 Bcl-2 的 mRNA 和蛋白表达。

结论

T140 通过阻断 SDF-1/CXCR4 信号通路在体外促进 CEP 细胞的增殖和基质形成,抑制细胞凋亡,为椎间盘退变提供了一定的治疗效果。

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