Streptococcus pyogenes degrades extracellular matrix in chondrocytes via MMP-13.
Group A streptococcus (GAS) causes a wide range of human diseases, including bacterial arthritis. The pathogenesis of arthritis is characterized by synovial proliferation and the destruction of cartilage and subchondral bone in joints. We report here that GAS strain JRS4 invaded a chondrogenic cell line ATDC5 and induced the degradation of the extracellular matrix (ECM), whereas an isogenic mutant of JRS4 lacking a fibronectin-binding protein, SAM1, failed to invade the chondrocytes or degrade the ECM. Reverse transcription-PCR and Western blot analysis revealed that the expression of matrix metalloproteinase (MMP)-13 was strongly elevated during the infection with GAS. A reporter assay revealed that the activation of the AP-1 transcription factor and the phosphorylation of c-Jun terminal kinase participated in MMP-13 expression. These results suggest that MMP-13 plays an important role in the destruction of infected joints during the development of septic arthritis.
Sakurai
Atsuo
A
Division 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.
Okahashi
Nobuo
N
Maruyama
Fumito
F
Ooshima
Takashi
T
Hamada
Shigeyuki
S
Nakagawa
Ichiro
I
D000818:Animals; D001170:Arthritis, Infectious / Q000201:enzymology*; D002460:Cell Line; D019902:Chondrocytes / Q000201:enzymology* / Q000382:microbiology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism* / Q000382:microbiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D051379:Mice; D013290:Streptococcal Infections / Q000201:enzymology*; D013297:Streptococcus pyogenes; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13