Matrix metalloproteinase-9 (gelatinase B) deficiency leads to increased severity of Staphylococcus aureus-triggered septic arthritis.
Matrix metalloproteinases constitute a family of structurally related endopeptidases that are crucial for the normal turnover of the extracellular matrix. Elevated levels of MMP-9 have been demonstrated in synovial fluids of rheumatoid arthritis patients, and a correlation with the severity of the disease has been described. The aim of this study was to explore the impact of MMP-9 expression on joint inflammation and destruction in a model of bacterially induced septic arthritis. MMP-9 knock-out mice and C57Bl6 congenic controls were inoculated intravenously or intra-articularly with Staphylococcus aureus. Arthritis was evaluated clinically and by means of histology. Zymographic analyses were performed to study ex vivo induction of MMP-9 following exposure to S. aureus. The MMP-9 knock-out mice displayed a significantly higher frequency and severity, but not destructivity, of arthritis than did the wild-type mice. The knock-out mice also proved to harbour an increased number of bacteria locally in joints and systemically in kidneys, possibly by impaired extravasation and recruitment of leukocytes and a deficient early defence against infection. Our findings indicate that deficiency in MMP-9 increases the degree of joint inflammation due to decreased bacterial clearance.
Calander
Ann-Marie
AM
Department of Rheumatology and Inflammation Research, University of Gothenburg, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden. ann-marie.calender@rheuma.gu.se
Starckx
Sofie
S
Opdenakker
Ghislain
G
Bergin
Philip
P
Quiding-Järbrink
Marianne
M
Tarkowski
Andrej
A
D000818:Animals; D001170:Arthritis, Infectious / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006651:Histocytochemistry; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*
D015850:Interleukin-6; D020780:Matrix Metalloproteinase 9