Tumor necrosis factor-α induces ADAMTS-4 expression in human osteoarthritis chondrocytes

Xue,Juan; Wang,Jianlong; Liu,Qiang; Luo,Aijing

doi:10.3892/mmr.2013.1729

Tumor necrosis factor-α induces ADAMTS-4 expression in human osteoarthritis chondrocytes

Authors:
- Juan Xue
- Jianlong Wang
- Qiang Liu
- Aijing Luo
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Affiliations: Department of Urology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Orthopaedics, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: October 14, 2013 https://doi.org/10.3892/mmr.2013.1729
Pages: 1755-1760

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Abstract

Tumor necrosis factor (TNF)-α and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) are important in osteoarthritis (OA) cartilage degradation. In the present study, we explored the interaction between the two proteins by examining the effect of TNF-α on ADAMTS-4 expression and activity in osteoarthritic chondrocytes. Human osteoarthritic chondrocytes were treated with TNF-α in different concentrations (5, 15, 30, 45 and 60 ng/ml) for different lengths of time (1, 6, 12, 18 and 24 h) with or without the TNF receptor 1 (TNFR1) inhibitor SPD304 or different kinase inhibitors. TNF-α increased the ADAMTS-4 mRNA level in a statistically significant dose- and time-dependent manner within 18 h, which was reflected in the dose-dependent induction of the ADAMTS-4 promoter activity, ADAMTS-4 protein expression and ADAMTS-4 activity. SPD304 (50 µM) and p38 mitogen-activated protein kinase (MAPK) siRNA and inhibitor PD169316 (25 µM) completely eradicated the promoting effect of TNF-α on ADAMTS-4 expression and activity. TNF-α induces ADAMTS-4 expression and activity in human osteoarthritic chondrocytes at the transcriptional level via TNFR1 by a p38 MAPK-dependent mechanism. To the best of our knowledge, this is the first evidence of crosstalk between TNF-α and ADAMTS-4 in relation to OA cartilage degradation, which adds novel insight into the pathophysiology of OA and cartilage degradation.

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