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Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down-regulation by tumor necrosis factor alpha blockade in spondylarthropathy.
Arthritis Rheum. 2004 Sep; 50(9):2942-53.AR

Abstract

OBJECTIVE

To investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in spondylarthropathy (SpA) synovitis.

METHODS

Paired samples of synovial biopsy tissue as well as serum and synovial fluid (SF) from 41 patients with SpA and 20 patients with rheumatoid arthritis (RA) and serum samples from 20 healthy controls were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay for the presence of MMPs 1, 2, 3, and 9 and TIMPs 1 and 2. In addition, sera from 16 patients with ankylosing spondylitis (AS) and peripheral synovitis and 17 patients with AS and exclusively axial involvement were analyzed. An additional cohort of SpA patients was analyzed at baseline and after 12 weeks of infliximab treatment.

RESULTS

Staining for MMPs and TIMPs showed a cellular and interstitial pattern in the synovial lining and sublining layers that was similar between the RA and SpA patients. Involvement of MMPs and TIMPs in SpA synovitis was suggested by the correlation with cellular infiltration, vascularization, and cartilage degradation. Higher serum levels of MMPs 3 and 9 were revealed in SpA and RA patients as compared with healthy controls. Production of MMP-3, but not MMP-9, in the serum reflected the presence of peripheral synovitis, as indicated by 1) the correlation between serum levels, SF levels (which were 1,000-fold higher than the serum levels), and synovial expression of MMP-3, 2) the increased levels of MMP-3 in AS patients with peripheral disease and not exclusively axial involvement, and 3) the correlation of serum and SF MMP-3 with parameters of synovial, but not systemic, inflammation. The modulation of the MMP/TIMP system by tumor necrosis factor alpha (TNFalpha) blockade was confirmed by the down-regulation of all MMPs and TIMPs in the synovium and a pronounced and rapid decrease of serum MMP-3.

CONCLUSION

MMPs and TIMPs are highly expressed in SpA synovitis and mirror both the inflammatory and tissue-remodeling aspects of the local disease process. Serum MMP-3, originating from the inflamed joint, represents a valuable biomarker for peripheral synovitis. Modulation of the MMP/TIMP system by infliximab could contribute to the antiinflammatory and tissue-remodeling effects of TNFalpha blockade in SpA.

Authors+Show Affiliations

Ghent University Hospital, Ghent, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15457463

Citation

Vandooren, Bernard, et al. "Involvement of Matrix Metalloproteinases and Their Inhibitors in Peripheral Synovitis and Down-regulation By Tumor Necrosis Factor Alpha Blockade in Spondylarthropathy." Arthritis and Rheumatism, vol. 50, no. 9, 2004, pp. 2942-53.
Vandooren B, Kruithof E, Yu DT, et al. Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down-regulation by tumor necrosis factor alpha blockade in spondylarthropathy. Arthritis Rheum. 2004;50(9):2942-53.
Vandooren, B., Kruithof, E., Yu, D. T., Rihl, M., Gu, J., De Rycke, L., Van Den Bosch, F., Veys, E. M., De Keyser, F., & Baeten, D. (2004). Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down-regulation by tumor necrosis factor alpha blockade in spondylarthropathy. Arthritis and Rheumatism, 50(9), 2942-53.
Vandooren B, et al. Involvement of Matrix Metalloproteinases and Their Inhibitors in Peripheral Synovitis and Down-regulation By Tumor Necrosis Factor Alpha Blockade in Spondylarthropathy. Arthritis Rheum. 2004;50(9):2942-53. PubMed PMID: 15457463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down-regulation by tumor necrosis factor alpha blockade in spondylarthropathy. AU - Vandooren,Bernard, AU - Kruithof,Elli, AU - Yu,David T Y, AU - Rihl,Markus, AU - Gu,Jieruo, AU - De Rycke,Leen, AU - Van Den Bosch,Filip, AU - Veys,Eric M, AU - De Keyser,Filip, AU - Baeten,Dominique, PY - 2004/10/1/pubmed PY - 2004/10/27/medline PY - 2004/10/1/entrez SP - 2942 EP - 53 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 50 IS - 9 N2 - OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in spondylarthropathy (SpA) synovitis. METHODS: Paired samples of synovial biopsy tissue as well as serum and synovial fluid (SF) from 41 patients with SpA and 20 patients with rheumatoid arthritis (RA) and serum samples from 20 healthy controls were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay for the presence of MMPs 1, 2, 3, and 9 and TIMPs 1 and 2. In addition, sera from 16 patients with ankylosing spondylitis (AS) and peripheral synovitis and 17 patients with AS and exclusively axial involvement were analyzed. An additional cohort of SpA patients was analyzed at baseline and after 12 weeks of infliximab treatment. RESULTS: Staining for MMPs and TIMPs showed a cellular and interstitial pattern in the synovial lining and sublining layers that was similar between the RA and SpA patients. Involvement of MMPs and TIMPs in SpA synovitis was suggested by the correlation with cellular infiltration, vascularization, and cartilage degradation. Higher serum levels of MMPs 3 and 9 were revealed in SpA and RA patients as compared with healthy controls. Production of MMP-3, but not MMP-9, in the serum reflected the presence of peripheral synovitis, as indicated by 1) the correlation between serum levels, SF levels (which were 1,000-fold higher than the serum levels), and synovial expression of MMP-3, 2) the increased levels of MMP-3 in AS patients with peripheral disease and not exclusively axial involvement, and 3) the correlation of serum and SF MMP-3 with parameters of synovial, but not systemic, inflammation. The modulation of the MMP/TIMP system by tumor necrosis factor alpha (TNFalpha) blockade was confirmed by the down-regulation of all MMPs and TIMPs in the synovium and a pronounced and rapid decrease of serum MMP-3. CONCLUSION: MMPs and TIMPs are highly expressed in SpA synovitis and mirror both the inflammatory and tissue-remodeling aspects of the local disease process. Serum MMP-3, originating from the inflamed joint, represents a valuable biomarker for peripheral synovitis. Modulation of the MMP/TIMP system by infliximab could contribute to the antiinflammatory and tissue-remodeling effects of TNFalpha blockade in SpA. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15457463/Involvement_of_matrix_metalloproteinases_and_their_inhibitors_in_peripheral_synovitis_and_down_regulation_by_tumor_necrosis_factor_alpha_blockade_in_spondylarthropathy_ L2 - https://doi.org/10.1002/art.20477 DB - PRIME DP - Unbound Medicine ER -