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Hypoxic induction of CCN2 mRNA through p38 MAP kinase activation in the human chondrosarcoma‐derived cell line, HCS‐2/8
Author(s) -
Yoshino Aya,
Hashiguchi Shiho,
Mano Ryosuke,
Kondo Seiji,
Kubota Satoshi,
Takigawa Masaharu
Publication year - 2021
Publication title -
oral science international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.256
H-Index - 13
eISSN - 1881-4204
pISSN - 1348-8643
DOI - 10.1002/osi2.1076
Subject(s) - ctgf , p38 mitogen activated protein kinases , mapk/erk pathway , kinase , messenger rna , hypoxia (environmental) , microbiology and biotechnology , protein kinase a , growth factor , cell culture , biology , mitogen activated protein kinase , chemistry , biochemistry , receptor , gene , genetics , organic chemistry , oxygen
Abstract CCN2/CTGF (cellular communication network factor 2/connective tissue growth factor) plays critical roles in cartilage development, maintenance, and regeneration. Hypoxia‐induced expression of CCN2 mRNA is regulated post‐transcriptionally in the human chondrosarcoma‐derived cell line, HCS‐2/8. In the present study, the hypoxia‐induced increase in CCN2 mRNA expression was assessed with quantitative real‐time PCR in HCS‐2/8 cells in the presence of inhibitors of mitogen‐activated protein kinases (MAPKs). Subsequently, the stability of CCN2 mRNA in hypoxia was evaluated with mRNA degradation assays in the presence or absence of the selective p38 MAPK inhibitor, SB203580. We detected phosphorylation of p38 MAPK by immunoblot analysis within 30 minutes in hypoxia, and we observed ~twofold higher CCN2 mRNA levels in hypoxia compared to normoxia. Blockade of p38 MAPK activation with 10 µmol/L SB203580 abolished this CCN2 induction. Furthermore, we found that inhibition of p38 MAPK suppressed the elongation of CCN2 mRNA half‐life in hypoxia. Taken together, these findings suggest that the molecular mechanism, by which CCN2 mRNA expression is increased in hypoxia, induces the activation of p38 MAPK leading to the post‐transcriptional regulation of the stability of CCN2 mRNA.