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

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.

The specific PKC-α inhibitor chelerythrine blunts costunolide-induced eryptosis

“…The pharmacokinetic profile of costunolide has been reported [8] and its therapeutic potential is supported by numerous animal studies. Costunolide possesses anti-angiogenic [9,10] and -osteoarthritic effects [11]. It inhibits pulmonary [12] and hepatic fibrosis [13], induces hair growth [14] and shows strong larvicidal activity [15].…”

Baicalin promotes extracellular matrix synthesis in chondrocytes via the activation of hypoxia‑inducible factor‑1α

“…) and ADAMTS5 are regarded as the key enzymes in the progression of OA that involves the breakdown of the ECM (31). Compared with respective control groups, the mRNA expression of ADAMTS5, MMP9, MMP13, PHD1, PHD2 and PHD3 in chondrocytes of BA-treated groups were significantly downregulated (P<0.01; Fig.…”

Platelet-Rich Plasma Combined with Alendronate Reduces Pain and Inflammation in Induced Osteoarthritis in Rats by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway

“…NF- κ B signaling pathway plays an important regulatory role in the occurrence and development of OA through maintaining the chondrocyte phenotype and balancing cartilage matrix metabolism [ 1 , 32 , 33 ]. Xue et al [ 34 ] have confirmed that LDC067 exerted protective effects in OA by inhibiting the NF- κ B signaling pathway.…”