Costunolide inhibits matrix metalloproteinases expression and osteoarthritis via the NF‑κB and Wnt/β‑catenin signaling pathways

He,Yuzhe; Moqbel,Safwat  Adel Abdo; Xu,Langhai; Ran,Jisheng; Ma,Chiyuan; Xu,Kai; Bao,Jiapeng; Jiang,Lifeng; Chen,Weiping; Xiong,Yan; Wu,Lidong

doi:10.3892/mmr.2019.10239

Costunolide inhibits matrix metalloproteinases expression and osteoarthritis via the NF‑κB and Wnt/β‑catenin signaling pathways

Authors:
- Yuzhe He
- Safwat Adel Abdo Moqbel
- Langhai Xu
- Jisheng Ran
- Chiyuan Ma
- Kai Xu
- Jiapeng Bao
- Lifeng Jiang
- Weiping Chen
- Yan Xiong
- Lidong Wu
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Affiliations: Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China
Published online on: May 14, 2019 https://doi.org/10.3892/mmr.2019.10239
Pages: 312-322
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is a chronic joint disease involving cartilage erosion and matrix degradation. Costunolide is a sesquiterpene lactone that has been demonstrated to exert anti‑inflammatory activities in a wide variety of cells. The aim of the present study was to investigate the effect of costunolide in OA treatment, using rat chondrocytes and an OA rat model, in which animals were subjected to destabilization of the medial meniscus. The results revealed that costunolide (2‑6 µM) had no effect on chondrocyte viability or phenotype maintenance. Costunolide decreased the interleukin (IL)‑1β‑induced upregulation of matrix metalloproteinases (MMPs), inducible nitric oxide synthase, cyclooxygenase‑2 and IL‑6, and increased the expression of collagen II and transcription factor SOX‑9, which were inhibited by IL‑1β. Costunolide significantly decreased p65 phosphorylation induced by IL‑1β and the translocation of p65 into the nucleus of rat chondrocytes, as observed by western blot analysis and immunofluorescence staining. In addition, activation of the Wnt/β‑catenin signaling pathway was inhibited by costunolide, as demonstrated by the level of activation of β‑catenin and the transfer of β‑catenin into the nucleus induced by IL‑1β. In vivo, cartilage treated with costunolide exhibited attenuated degeneration and lower Mankin scores compared with the OA group. The present study investigated the anti‑osteoarthritic effects of costunolide, which exerted anti‑inflammatory activities and inhibited MMPs expression. Taken together, these results indicate that costunolide may have a potential value in the treatment of OA.

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