Inhibition against p38/MEF2C pathway by Pamapimod protects osteoarthritis chondrocytes hypertrophy.

IF 4.3 4区医学 0 MEDICINE, GENERAL & INTERNAL Panminerva medica Pub Date : 2024-12-01 Epub Date: 2020-12-02 DOI:10.23736/S0031-0808.20.04170-1

Jian Zhang, Chen Yan, Weidong He, Min Wang, Jian Liu

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Abstract

Background: The p38 mitogen-activated protein kinase pathway plays an important role in the pathogenesis of osteoarthritis (OA) involving in hypertrophy, calcification, and apoptosis of chondrocytes (CHs). In this study, we focused on a p38 inhibitor named Pamapimod (PAM) in the effect of CH hypertrophy degeneration.

Methods: CHs were isolated from the cartilage collected from OA patients. Insulin-Transferrin-Selenium (ITS) medium was used as a hypertrophic inducer to establish CH hypertrophy model. Asiatic acid (AA) was used to activate p38 phosphorylation. We transfected CHs with myocyte enhancer factor 2C (MEF2C)-plasmid to upregulate MEF2C expression. Chondrogenic gene expression such as type II collagen and SOX-9, and hypertrophic genes such as type X collagen, MMP-13, and Runx-2 were analyzed by western blot, real-time polymerase chain reaction or immunofluorescence.

Results: ITS and AA all contributed to the CHs hypertrophy with an upregulation of p-p38 and MEF2C protein expression. PAM treatments significantly inhibited p-p38 and MEF2C expression, down-regulated type X collagen, MMP-13, and Runx-2 expression and upregulated type II collagen and SOX-9 levels. PAM indirectly affected MEF2C expression and resulted in CHs hypertrophy suppression.

Conclusions: PAM protects CHs hypertrophy by the inhibition of the p38/MEF2C pathway.

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帕马匹莫德抑制 p38/MEF2C 通路可保护骨关节炎软骨细胞肥大。

背景：p38丝裂原活化蛋白激酶通路在骨关节炎（OA）的发病机制中起着重要作用，涉及软骨细胞（CHs）的肥大、钙化和凋亡。在这项研究中，我们重点研究了一种名为帕马匹莫德（PAM）的 p38 抑制剂对 CH 肥厚变性的影响：方法：从 OA 患者的软骨中分离出 CHs。胰岛素-转铁蛋白-硒（ITS）培养基作为肥大诱导剂，建立CH肥大模型。使用积雪草酸（AA）激活p38磷酸化。我们用肌细胞增强因子2C（MEF2C）质粒转染CH，以上调MEF2C的表达。通过Western印迹、RT-PCR或免疫荧光分析了软骨生成基因（如II型胶原和SOX-9）和肥大基因（如X型胶原、MMP-13和Runx-2）的表达：结果：ITS和AA都会导致CHs肥大，并上调p-p38和MEF2C蛋白的表达。PAM处理可明显抑制p-p38和MEF2C的表达，下调X型胶原、MMP-13和Runx-2的表达，上调II型胶原和SOX-9的水平。PAM 间接影响了 MEF2C 的表达，抑制了 CHs 的肥大：结论：PAM 通过抑制 p38/MEF2C 通路保护 CHs 肥大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Panminerva medica 医学-医学：内科

CiteScore

5.00

自引率

2.30%

发文量

199

审稿时长

>12 weeks

期刊介绍： Panminerva Medica publishes scientific papers on internal medicine. Manuscripts may be submitted in the form of editorials, original articles, review articles, case reports, special articles, letters to the Editor and guidelines. The journal aims to provide its readers with papers of the highest quality and impact through a process of careful peer review and editorial work. Duties and responsibilities of all the subjects involved in the editorial process are summarized at Publication ethics. Manuscripts are expected to comply with the instructions to authors which conform to the Uniform Requirements for Manuscripts Submitted to Biomedical Editors by the International Committee of Medical Journal Editors (ICMJE).