Cell Stress and Chaperones

, Volume 23, Issue 3, pp 393–398 | Cite as

Interferonregulatoryfactor-8(IRF-8) regulates the expression of matrix metalloproteinase-13 (MMP-13) in chondrocytes

  • Qining Yang
  • Weiguo Ding
  • Yang Cao
  • Yongwei Zhou
  • Shuo Ni
  • Tiejun Shi
  • Weicong Fu
Original Paper
  • 58 Downloads

Abstract

Low levels of inflammation-induced expression of matrix metalloproteinase (MMP) play a crucial role in articular cartilage matrix destruction in osteoarthritis (OA) patients. Interferon regulatory factor-8 (IRF-8), an important member in the IRF family, plays a key role in regulating the inflammation-related signaling pathway. The aim of this study is to investigate the physiological roles of IRF-8 in the pathological progression of OA. We found that IRF-8 was expressed in human primary chondrocytes. Interestingly, the expression of IRF-8 was upregulated in OA chondrocytes. In addition, IRF-8 was increased in response to interleukin-1β (IL-1β) treatment, mediated by the Janus kinase 2 (JAK2) pathway. Overexpression of IRF-8 in human chondrocytes by transduction with lentiviral-IRF-8 exacerbated IL-1β-induced expression of matrix metalloproteinase-13 (MMP-13) in human chondrocytes. In contrast, knockdown of IRF-8 inhibited IL-1β-induced expression of MMP-13. Importantly, IRF-8 could bind to the promoter of MMP-13 and stimulate its activity. Additionally, overexpression of IRF-8 exacerbated IL-1β-induced degradation of type II collagen. However, silencing IRF-8 abrogated the degradation of type II collagen. Taken together, our findings identified a novel function of IRF-8 in regulating articular cartilage matrix destruction by promoting the expression of MMP-13.

Keywords

Osteoarthritis Interferon regulatory factor-8 Matrix metalloproteinases Type II collagen 

Notes

Compliance with ethical standards

Ethics statement

Human subject research protocols were in accordance with the world medical association declaration of the Helsinki Ethical Principles for Medical Research involving human subjects. All of the participants signed a written informed consent.

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Copyright information

© Cell Stress Society International 2017

Authors and Affiliations

  • Qining Yang
    • 1
  • Weiguo Ding
    • 2
  • Yang Cao
    • 1
  • Yongwei Zhou
    • 1
  • Shuo Ni
    • 1
  • Tiejun Shi
    • 1
  • Weicong Fu
    • 1
  1. 1.Department of Joint Orthopaedic Surgery, Jinhua Municipal Central HospitalJinhua Hospital of Zhejiang UniversityJinhuaPeople’s Republic of China
  2. 2.Department of OrthopaedicsTongde Hospital of Zhejiang ProvinceHangzhouPeople’s Republic of China

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