Celecoxib Combined with Diacerein Effectively Alleviates Osteoarthritis in Rats via Regulating JNK and p38MAPK Signaling Pathways

Li, Zhifu; De-sheng, Meng; Li, Guangheng; Xu, Jianzhong; Tian, Kui; Liu, Yu

doi:10.1007/s10753-015-0131-3

Cited by 30 publications

(24 citation statements)

References 36 publications

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“…In endothelial cells, the JNK signaling pathway specifically mediates the expression of cyclooxygenase-2 (Cox-2) and matrix metalloproteinase-13 (MMP-13) in response to a variety of cytokines (34,35). As revealed by RT-PCR, Cox-2 and MMP-13 transcription was significantly increased in HUVECs following treatment with 20 µM DHA for 24 h (P=0.010 and P=0.020, respectively; Fig.…”

Section: Dha Induces the Expression Of The Downstream Genes Of The Jnmentioning

confidence: 93%

Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells

et al. 2016

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Abstract. Artemisinin and its derivatives are well-known anti-malaria drugs and in the early stages of research for cancer treatment. Dihydroartemisinin (DHA), a more water-soluble derivative of artemisinin, has demonstrated strong anti-angiogenic activity. The purpose of the present study was to investigate the underlying molecular mechanisms of the effect of DHA on angiogenesis. Human umbilical vein endothelial cells (HUVECs) treated with DHA were examined for apoptosis and activation of the c-Jun N-terminal kinase (JNK) signaling pathway, one of the major mitogen-activated protein kinase cascades. It was observed that 20 µM DHA induces transient activation of JNK in HUVECs. DHA also elevates the expression of cyclooxygenase-2 and matrix metalloproteinase-13, which is abolished by treatment with the JNK inhibitor SP600125. Although DHA persistently increases inhibitor of κB-α protein and thus inhibits nuclear factor-κB signaling, it does not affect apoptosis or caspase 3/9 activities in HUVECs. The present study provides key information for understanding the effects of DHA on endothelial cells, which is required for investigating its potential for clinic application as a chemotherapeutic agent.

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Section: Dha Induces the Expression Of The Downstream Genes Of The Jnmentioning

confidence: 93%

Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells

et al. 2016

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“…NO can induce cartilage matrix degradation by suppressing proteoglycan synthesis, activating MMPs, and inducing cartilage degradation 31 . Zweers et al showed that celecoxib inhibited NO depending on the chondrocyte cell culture model 6 , and some studies did not confirm NO suppression by celecoxib 19e21, 32 . A rat arthritis model reviewed showed better OA attenuation with celecoxib and anthraquinone diacerein combination than either drug alone.…”

Section: Effects On Cytokines/mmpmentioning

confidence: 99%

Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: a systematic review

Nakata

Hanai

Take

et al. 2018

Osteoarthritis and Cartilage

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Osteoarthritis (OA) is a potentially disabling disease whose progression is dependent on several risk factors. OA management usually involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) that are the primary pharmacological treatments of choice. However, NSAIDs have often been associated with unwanted side effects. Cyclooxygenase (COX)-2 specific inhibitors, such as celecoxib, have been successfully used as an alternative in the past for OA treatment and have demonstrated fewer side effects. While abundant data are available for the clinical efficacy of drugs used for OA treatment, little is known about the disease-modifying effects of these agents. A previous review published by Zweers et al. (2010) assessed the available literature between 1990 and 2010 on the disease-modifying effects of celecoxib. In the present review, we aimed to update the existing evidence and identify evolving concepts relating to the disease-modifying effects of not just celecoxib, but also other NSAIDs. We conducted a review of the literature published from 2010 to 2016 dealing with the effects, especially disease-modifying effects, of NSAIDs on cartilage, synovium, and bone in OA patients. Our results show that celecoxib was the most commonly used drug in papers that presented data on disease-modifying effects of NSAIDs. Further, these effects appeared to be mediated through the regulation of prostaglandins, cytokines, and direct changes to tissues. Additional studies should be carried out to assess the disease-modifying properties of NSAIDs in greater detail.

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“…As a result of the poor self-repair ability of cartilage, preventing COL2 degradation in cartilage injury is the key factor in inhibiting further cartilage degeneration and OA progression (12). Interleukin (IL)-1β is the most important proinflammatory cytokine in the pathophysiology of OA, which serves a key role in COL2 degradation (13,14). It has been reported that IL-1β could upregulate the Wnt5a protein, and the Wnt5a protein could activate the Jun amino-terminal kinase (JNK) signaling pathway, inducing the upregulation of matrix metalloproteinases (MMPs) (15,16).…”

Section: Introductionmentioning

confidence: 99%

Silencing of Wnt5a prevents interleukin-1β-induced collagen type II degradation in rat chondrocytes

Shi

Man

et al. 2016

Experimental and Therapeutic Medicine

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Osteoarthritis (OA) is a joint disease, and few treatments to date have been able to delay OA progression. The degradation of collagen type II (COL2) in the cartilage matrix is an important initiating factor for OA progression; the upregulation of Wnt5a protein activates COL2 degradation. In the present study, small interfering RNA of Wnt-5a was delivered by a lentiviral vector (LV-Wnt5a-RNAi) to silence Wnt-5a mRNA and prevent COL2 degradation. To determine the function of LV-Wnt5a-RNAi, the OA chondrocyte model (OA-like chondrocytes) were constructed using interleukin (IL)-1β. Detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Wnt-5a mRNA in the OA-like chondrocytes were upregulated in a time-dependent manner, indicating that OA-like chondrocytes were successfully constructed. The bioactivity of OA-like chondrocytes was determined using Live-Dead staining, and the result illustrated that the OA-like chondrocytes stimulated with IL-1β for 6 h remained viable, and these were used in Wnt5a silencing. The OA-like chondrocytes were divided into three groups: Group I, cultivated with common medium; group II, cultivated with common medium supplemented with empty lentiviral vector; group III, cultivated with common medium supplemented with LV-Wnt5a-RNAi. The efficiency of LV-Wnt5a-RNAi transfection was determined using fluorescence microscopy, the result of which indicated that LV-Wnt5a-RNAi could efficiently be transfected into the OA-like chondrocytes. The LV-Wnt5a-RNAi efficiency for the Wnt5a mRNA silencing was determined using RT-qPCR. The result illustrated that the mRNA of Wnt5a in group III was significantly lower in group I compared with that in group II (P<0.05), indicating that the LV-Wnt5a-RNAi could successfully silence Wnt5a mRNA. To further verify whether the silencing of Wnt5a mRNA could prevent COL2 degradation, western blotting and immunohistochemical analyses were performed. The results demonstrated that COL2 in group III was significantly higher compared with that in groups I and II (P<0.05), which illustrated that the silencing of Wnt5a mRNA could prevent COL2 degradation. In conclusion, LV-Wnt5a-RNAi was formed successfully and could efficiently silence Wnt5a mRNA expressed by OA-like chondrocytes. In addition, the silencing of Wnt5a mRNA could prevent the degradation of COL2 in OA-like chondrocytes, confirming that LV-Wnt5a-RNAi may be used as a novel tool for OA treatment.

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Celecoxib Combined with Diacerein Effectively Alleviates Osteoarthritis in Rats via Regulating JNK and p38MAPK Signaling Pathways

Cited by 30 publications

References 36 publications

Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells

Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells

Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: a systematic review

Silencing of Wnt5a prevents interleukin-1β-induced collagen type II degradation in rat chondrocytes

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