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Panminerva Medica 2020 Dec 02

DOI: 10.23736/S0031-0808.20.04170-1

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

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

Jian ZHANG 1, Chen YAN 1, Weidong HE 1, Min WANG 2, Jian LIU 1

1 Department of Orthopaedics, The First People’s Hospital of Lianyungang, Lianyungang, China; 2 Department of Medicine, The First People’s Hospital of Lianyungang, Lianyungang, China


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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, RT-PCR 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.


KEY WORDS: p38; MEF2C; Chondrocyte; Hypertrophy; Osteoarthritis

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