Baicalein Inhibits MMPs Expression via a MAPK-Dependent Mechanism in Chondrocytes

Self Cite

Background: Osteoarthritis (OA) is a joint disease in which cartilage degradation is the central pathological change. In this study, we investigated the anti-osteoarthritic effects of licochalcone A (Lico A) in rat chondrocytes. Methods: Polymerase chain reaction and Western blotting were performed to evaluate the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, ADAMTS-4, collagen II, matrix metalloproteinase (MMP)-13 and MMP-1 at both the gene and protein levels, respectively. In addition, the wnt/β-catenin and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by Western blotting. Results: Lico A downregulated ADAMTS-5, ADAMTS-4,MMP-13 and MMP-1 expression, and diminished the IL-1β-induced inhibition of collagen II. In addition, the activation of β-catenin and phosphorylation of p65 and IKKα/β were suppressed by Lico A. Conclusions: Our results suggest that Lico A inhibits MMPs and ADAMTS partly via the NF-κB and wnt/β-catenin signaling pathways in rat chondrocytes. Thus, Lico A may have therapeutic effects in OA.

Section: Discussionmentioning

confidence: 81%

Licochalcone A Inhibits MMPs and ADAMTSs via the NF-κB and Wnt/β-Catenin Signaling Pathways in Rat Chondrocytes

Chen

Jin

et al. 2017

Self Cite

“…However, it has been well established that miRNAs is involved in OA. Several miRNAs have been identified as having aberrant expression levels in osteoarthritis, such as miR-9, miR-27, miR-34a, miR-140, miR-146a, miR-558 and miR-602[7, 19, 24]. Increasing amounts of evidence have indicated that there is an existing link between miRNAs and osteoarthritis in the pathogenesis of OA.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA CIR Promotes Chondrocyte Extracellular Matrix Degradation in Osteoarthritis by Acting as a Sponge For Mir-27b

Li¹,

Li²,

Liu³

et al. 2017

Background/Aims: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. The degradation of the extracellular matrix (ECM) of chondrocyte is closely associated with the destruction of joints in OA patients. lncRNAs are non-coding segments of RNA that possess important regulatory functions at the cellular level and in a variety of pathophysiological processes. The present study was conducted to investigate whether lncRNA-CIR regulated the expression of MMP13 as a sponge of miR-27 in OA. Methods: Primary cultured chondrocytes were challenged by IL-1β and TNF-α to simulate OA conditions. qRT-PCR was performed to detect the miR-27, lncRNA-CIR, MMP13 mRNA expression levels. Western blot was applied to detect MMP13 protein expression. Soluble sGAG secretion/ formation was analysed by the dimethylmethylene blue (DMMB) assay. lncRNA-CIR overexpression or inhibition was performed using overexpression plasmid and small interfering RNAs (siRNAs), respectively. Results: lncRNA-CIR significantly up-regulated in OA patients, concomitantly down-regulated miR-27 and up-regulated MMP13. Bioinformatics analysis predicted miR-27 was the target of both lncRNA-CIR and MMP13. Overexpression of lncRNA-CIR significantly increased the expression of MMP13, while miR-27 remarkably suppressed the expression of MMP13, Accompanying with the increases of mRNA level, protein level and relative luciferase activity. Conclusion: The present findings indicated that lncRNA-CIR/miR-27/MMP13 axis involved in the degradation of the ECM of chondrocyte in OA.

“…Notably, IL-1β promotes degradation of certain components of the cartilage extracellular matrix, such as type II collagen, and disrupts cartilage integrity [7]. Therefore, disrupting the activity of pro-inflammatory cytokines and subsequent MMP-13 expression has become an important strategy for reducing cartilage degradation in OA [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13

Yuan¹,

Tan²,

Dai³

2017

Background/Aims: Krüppel-like factor 2 (KLF2) plays an essential role in the inhibition of endothelial cell and macrophage activation during the inflammatory process. However, the roles of KLF2 in chondrocytes and the pathological progression of osteoarthritis (OA) remain unknown. The aim of this study was to investigate the function of KLF2 in the inhibition of cartilage matrix destruction in chondrocytes. Methods: RT-PCR and western blot analysis was used to determine the expression of KLF2 in human chondrocytes. Luciferase assay, ELISA assay and MMP-13 enzymatic activity assays were used to investigate the effects of KLF2 in regulating MMP-13 expression. Western blot analysis was used to examine the effects of KLF2 in suppressing degradation of type Ⅱ collagen. Results: KLF2 is expressed in primary chondrocytes and is downregulated in OA chondrocytes. Expression of KLF2 in primary chondrocytes was reduced in response to IL-1β. Overexpression of KLF2 robustly inhibited IL-1β-induced MMP-13 expression. Conversely, knockdown of KLF2 markedly exacerbated MMP-13 expression. Mechanistically, KLF2 could suppress the activation of MMP-13 promoter. However, knockdown of KLF2 could promote the activation of MMP-13 promoter. Importantly, overexpression of KLF2 ameliorated the degradation of type Ⅱ collagen while silencing of KLF2 exacerbated the degradation of type Ⅱ collagen induced by IL-1β. Conclusions: KLF2 may be a potential therapeutic target for OA treatment.