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Updated: Aug 8, 2026

A Pre-Clinical Model of Synovitis Using Ex vivo Human Synovial Tissue with Preserved Function and Architecture
Published on: March 20, 2026
Matrix metalloproteinase-9 (gelatinase B) deficiency leads to increased severity of Staphylococcus aureus-triggered
Ann-Marie Calander1, Sofie Starckx, Ghislain Opdenakker
1Department of Rheumatology and Inflammation Research, University of Gothenburg, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden. ann-marie.calender@rheuma.gu.se
Abstract:
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.
Insights
Mice lacking matrix metalloproteinase-9 (MMP-9) showed worse septic arthritis, indicating MMP-9 is vital for clearing bacteria and controlling joint inflammation.
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Matrix metalloproteinases (MMPs) are enzymes critical for extracellular matrix turnover.
- Elevated MMP-9 levels correlate with rheumatoid arthritis severity.
- Septic arthritis involves bacterial infection leading to joint inflammation and destruction.
Purpose of the Study:
- To investigate the role of MMP-9 in bacterial-induced septic arthritis.
- To determine MMP-9's impact on joint inflammation and destruction.
- To assess bacterial clearance mechanisms in the absence of MMP-9.
Main Methods:
- Utilized MMP-9 knock-out mice and wild-type controls.
- Induced septic arthritis via Staphylococcus aureus inoculation (intravenous and intra-articular).
- Evaluated arthritis clinically and histologically; performed zymographic analyses for MMP-9 activity.
Main Results:
- MMP-9 knock-out mice exhibited increased frequency and severity of arthritis compared to controls.
- Absence of MMP-9 led to higher bacterial loads in joints and kidneys.
- Knock-out mice showed impaired leukocyte recruitment and bacterial clearance, suggesting a role in early defense.
Conclusions:
- MMP-9 deficiency exacerbates joint inflammation in septic arthritis due to reduced bacterial clearance.
- MMP-9 plays a protective role in managing bacterial infections within joints.
- Findings highlight MMP-9's importance in host defense against Staphylococcus aureus-induced arthritis.
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