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

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Abstract

Osteoarthritis (OA) has long been a difficult to overcome joint disease for medical workers. However, there is still a lack of effective treatments for OA. In the present study, we aimed to evaluate the treatment effect of celecoxib (CLX) combined with diacerein (DC) on OA and delineate the underlying molecular mechanism. The OA model was established by using rats, and OA rats were treated with either CLX alone, DC alone, and CLX combined with DC. The results showed that, as compared with a single treatment of CLX or DC, CLX combined with DC markedly attenuated OA and inhibited the levels of inflammatory mediators interleukin-1β and nitric oxide, improved bone cartilage metabolism, and suppressed chondrocyte apoptosis. Most importantly, CLX combined with DC significantly inactivated the c-Jun N-terminal kinases (JNK) signaling pathway by the inhibition of MEKK1 and MKK7, as detected by Western blot analysis. Furthermore, the protein expression of downstream genes of JNK, including activating-transcription factor (Atf-2), matrix metalloproteinase-13 (MMP-13), and cyclooxygenase (COX-2), were also significantly inhibited by CLX combined with DC as compared with single treatments. Furthermore, CLX combined with DC also effectively inhibits p38 mitogen-activated protein kinase and nuclear factor-κB signaling pathways. Taken together, our study suggests that CLX combined with DC has satisfactory treatment effects on OA via a stronger inhibitory effect on inflammatory signaling pathway.

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Abbreviations

OA:

Osteoarthritis

MMP-13:

Matrix metalloproteinase-13

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor α

CTX-II:

C-telopeptide fragments of type II collagen

MAPKs:

Mitogen-activated protein kinases

JNK:

c-Jun N-terminal kinases

Atf-2:

Activating-transcription factor

COX-2:

Cyclooxygenase

MAPK:

Mitogen-activated protein kinase

NSAID:

Non-steroidal anti-inflammatory drug

CLX:

Celecoxib

DC:

Diacerein

ELISA:

Enzyme-linked immune sorbent assay

BMD:

Bone mineral density

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, 450052, Zhengzhou, Henan, People’s Republic of China

    Zhifu Li, Guangheng Li, Jianzhong Xu, Ke Tian & Yu Li

  2. Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, People’s Republic of China

    Dongdong Meng

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  1. Zhifu Li
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Correspondence to Zhifu Li.

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Li, Z., Meng, D., Li, G. et al. Celecoxib Combined with Diacerein Effectively Alleviates Osteoarthritis in Rats via Regulating JNK and p38MAPK Signaling Pathways. Inflammation 38, 1563–1572 (2015). https://doi.org/10.1007/s10753-015-0131-3

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