J Biol Regul Homeost Agents. 2020 May-Jun;34(3):785-794. doi: 10.23812/20-78-A-8.


ORIGINAL ARTICLE


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Cyclooxygenase-2 inhibitor rofecoxib prevents chondrocytes against hypertrophy via Wnt/β-catenin pathway.

Yang YR#1, Yang XF#1, Duan HC1, Qiao JQ2.

Author information

1 Department of Gastroenterology, Gansu Gem Flower Hospital, Lanzhou, China.
2 Department of Orthopaedic, Gansu Gem Flower Hospital, Lanzhou, China.
# Contributed equally

Abstract

Previous reports indicated that specific cyclooxygenase-2 (COX-2) inhibitor suppresses osteoarthritis (OA). This study aimed to further explore the possible mechanism of Rofecoxib as a COX-2 inhibitor on the inhibition of chondrocyte (CH) hypertrophic development and tested the optimal treatment of Rofecoxib on CH. Basically, IL-1β was used as a stimulus to establish a degenerated CH model. Immunofluorescence, Western blot, and RT-PCR were performed to determine the gene expression of Axin2, β-catenin, GSK3β, collagen X, collagen II, COX-2, PGE-2, SOX-9, Runx-2, and MMP- 13 expression. Cell Counting Kit (CCK-8) assay was used to analyze the viability of CHs. The data indicated that Rofecoxib significantly inhibited COX-2 expression and had less harmful effects on CH viability. Rofecoxib reversed the IL-1β-induced upregulation of collagen X, COX-2, PGE-2, Runx-2, and MMP-13 expression, and promoted the viability of collagen II, SOX-9 expression of CHs. Furthermore, Rofecoxib suppressed Axin2, β-catenin, and GSK3β expression of the Wnt pathway, which was activated by IL-1β or human recombinant Wnt-1 protein treatment. Therefore, Rofecoxib is an effective COX-2 inhibitor that protects CHs from hypertrophy by suppression of the Wnt/β-catenin pathway.

KEYWORDS:

Rofecoxib; Wnt/β-catenin; chondrocyte hypertrophy; cyclooxygenase-2 inhibitor

Publication type

  • Journal Article

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