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Inflammation

, Volume 38, Issue 4, pp 1563–1572 | Cite as

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

  • Zhifu Li
  • Dongdong Meng
  • Guangheng Li
  • Jianzhong Xu
  • Ke Tian
  • Yu Li
Article

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.

KEY WORDS

celecoxib diacerein JNK signaling pathway osteoarthritis 

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

Notes

Conflict of Interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Zhifu Li
    • 1
  • Dongdong Meng
    • 2
  • Guangheng Li
    • 1
  • Jianzhong Xu
    • 1
  • Ke Tian
    • 1
  • Yu Li
    • 1
  1. 1.Department of Orthopaedic SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouPeople’s Republic of China
  2. 2.Department of EndocrinologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouPeople’s Republic of China

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