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Streptococcus pyogenes degrades extracellular matrix in chondrocytes via MMP-13

Atsuo Sakurai1, Nobuo Okahashi, Fumito Maruyama

  • 1Division of Bacteriology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

Biochemical and Biophysical Research Communications
|July 1, 2008
PubMed

Insights

Group A Streptococcus (GAS) invasion of joint cells triggers extracellular matrix degradation. A fibronectin-binding protein (SAM1) is crucial for this process, highlighting its role in septic arthritis.

Area of Science:

  • Microbiology
  • Immunology
  • Pathology

Background:

  • Group A Streptococcus (GAS) is a significant human pathogen responsible for various diseases, including septic arthritis.
  • Septic arthritis pathogenesis involves synovial proliferation and joint tissue destruction (cartilage, subchondral bone).

Purpose of the Study:

  • To investigate the role of GAS strain JRS4 and its fibronectin-binding protein, SAM1, in chondrocyte invasion and extracellular matrix (ECM) degradation.
  • To elucidate the molecular mechanisms, particularly matrix metalloproteinase (MMP)-13 expression, involved in GAS-induced joint damage.

Main Methods:

  • Invasion assays using a chondrogenic cell line (ATDC5) infected with GAS strain JRS4 and its isogenic SAM1 mutant.
  • Reverse transcription-PCR and Western blot analysis to assess MMP-13 expression levels.
  • Reporter assays to evaluate the involvement of AP-1 transcription factor and c-Jun terminal kinase (JNK) signaling in MMP-13 regulation.

Main Results:

  • GAS strain JRS4 successfully invaded ATDC5 chondrocytes and induced ECM degradation.
  • An isogenic GAS mutant lacking the fibronectin-binding protein SAM1 was unable to invade chondrocytes or degrade ECM.
  • MMP-13 expression was significantly upregulated during GAS infection.
  • AP-1 activation and JNK phosphorylation were identified as key mediators of MMP-13 expression.

Conclusions:

  • The fibronectin-binding protein SAM1 of GAS is essential for chondrocyte invasion and subsequent ECM destruction.
  • MMP-13 plays a critical role in the joint tissue damage observed in septic arthritis caused by GAS.
  • The AP-1/JNK signaling pathway is involved in regulating MMP-13 expression during GAS infection.

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