Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation

Akasaki, Yukio; Matsuda, Shuichi; Nakayama, Koichi; Fukagawa, Shingo; Miura, Hiromasa; Iwamoto, Yukihide

doi:10.1016/j.joca.2008.06.012

Cited by 67 publications

(80 citation statements)

References 45 publications

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“…This model induces instability of joint, resulting in typical OA-like lesions. The model is widely used in studies with pharmacological agents for OA [34,35]. Variable cartilage degeneration was detected in the present study, supporting the reliability and repeatability of the model.…”

Section: Discussionsupporting

confidence: 84%

Trichostatin A inhibits expression of cathepsins in experimental osteoarthritis

et al. 2010

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The aim of this study was to investigate the effects of trichostatin A (TSA) on expression of cathepsins in cartilage in experimental osteoarthritis (OA). OA was induced in 18 rabbits by bilateral anterior cruciate ligament transection (ACLT). Four weeks after surgery, rabbits received intra-articular injection with TSA dissolved in the dimethylsulphoxide (DMSO) in the right knees and DMSO in the left knees once a week for 5 weeks. Rabbits were killed 7 days after the last injection. The knee joints were assessed by morphological and histological examination. Messenger RNA expression of cathepsins K, B, L, S and cystatin C was studied by real-time PCR. TSA inhibited the expression of cathepsins K, B, L, S and cystatin C accompanied with the less degradation in cartilage. The results suggest that TSA exhibits protective effects against cartilage degradation in rabbits with OA and the effects may be associated with the inhibition of cathepsins.

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Section: Discussionsupporting

confidence: 84%

Trichostatin A inhibits expression of cathepsins in experimental osteoarthritis

et al. 2010

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“…We investigated the in vivo effects of baicalein on cartilage in experimental OA over a period of 6 weeks, which is similar to the durations used in previous studies [26,27]. We found that the cartilage displayed OA-like changes; Therefore, 6 weeks was sufficient to induce OA using ACLT.…”

Section: Discussionmentioning

confidence: 83%

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

Chen

Xiong

et al. 2015

Cell Physiol Biochem

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Background: Baicalein is a flavonoid isolated from Scutellaria baicalensis Georgi. Here, we investigated the anti-osteoarthritic effect of baicalein in vitro and in vivo. Methods: Interleukin-1 beta (IL-1β)-induced chondrocytes were treated with different concentrations of baicalein, real-time PCR and ELISA were performed to detect the matrix metalloproteinases (MMPs) expression. Western blot was used to evaluate the mitogen-activated protein kinase (MAPK) expression. In experimental osteoarthritis (OA), rabbits were treated with baicalein, gross morphological and histological assessment was performed to evaluate the cartilage damage. Results: Baicalein significantly reduced the expression of MMPs in vitro and in vivo. Moreover, baicalein significantly reduced the phosphorylation of p38 and extracellular signal regulated kinase (ERK), but not of c-Jun N-terminal kinase (JNK). In addition, intra-articular injection of baicalein ameliorated the cartilage damage in a rabbit model of OA induced by anterior cruciate ligament transection (ACLT). Conclusions: The results indicate that baicalein may be considered as a potential agent for OA treatment.

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“…Studies have demonstrated that NF-κB triggers the expression of an array of genes that induce destruction of the articular joints, thereby leading to the onset and progression of OA. Interestingly, NF-κB has been reported to regulate the effects of IL-1β on the transcription of MMP-13 in human chondrocytes [26]. The anti-inflammatory capacity of KLF2 has been widely correlated to its inhibitory effects on the binding ability of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, multiple lines of evidence have shown that the atheroprotective effects and cholesterol-lowering abilities of statins are mediated by KLF2 [25]. Interestingly, mevastatin, a member of the statin family, has been proven to reduce inflammatory cell infiltration and cartilage degradation by suppressing the expression of IL-1β, MMP-3, and MMP-13 in rabbit synovial tissues [26]. In addition, KLF2 has been reported to be involved in the anti-inflammatory ability of montelukast, another licensed drug clinically used for the treatment of asthma [29].…”

Section: Discussionmentioning

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

Cell Physiol Biochem

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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.

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Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation

Abstract: During the development of experimental OA, intra-articular administration of HMG-CoA reductase inhibitor (statin) reduces inflammatory cell infiltration and matrix-degrading enzyme expression, thus limiting cartilage degradation.

Cited by 67 publications

References 45 publications

Trichostatin A inhibits expression of cathepsins in experimental osteoarthritis

Trichostatin A inhibits expression of cathepsins in experimental osteoarthritis

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

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

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