Stimulation of collagenase 3 expression in synovial fibroblasts of patients with rheumatoid arthritis by contact with a three-dimensional collagen matrix or with normal cartilage when coimplanted in NOD/SCID mice

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Item Type:	Article
Title:	Stimulation of collagenase 3 expression in synovial fibroblasts of patients with rheumatoid arthritis by contact with a three-dimensional collagen matrix or with normal cartilage when coimplanted in NOD/SCID mice
Creators Name:	Wernicke, D., Schulze-Westoff, C., Petrow, P., Brauer, R., Zacher, J., Gay, S. and Gromnica-Ihle, E.
Abstract:	Objective. To study the expression of collagenase 3 (matrix metalloproteinase 13 [MMP-13]) and collagenase 1 (MMP-1) in synovial fibroblasts from patients with rheumatoid arthritis (RA) when cultured within 3-dimensional collagen gels or coimplanted with normal cartilage in immunodeficient NOD/SCID mice. Methods. Messenger RNA (mRNA) and protein expression of collagenase 3 and collagenase 1 were characterized in synovial and skin fibroblasts by Northern blot and Western blot analysis. The mRNA expression of both collagenases in cell-cartilage implants in NOD/SCID mice was investigated by in situ hybridization in combination with immunohistochemistry of human fibroblasts. Results. Synovial fibroblasts coimplanted with normal cartilage in NOD/SCID mice deeply invaded adjacent cartilage tissue. In this in vivo system of cartilage destruction, collagenase 3 mRNA was induced in synovial fibroblasts at sites of cartilage erosion, while the expression of collagenase 1 mRNA could not be detected. Culture of synovial fibroblasts within 3-dimensional collagen gels was associated with a marked increase in collagenase 3 mRNA expression and proenzyme production. This stimulatory effect was 1 order of magnitude higher in comparison with a 2-4-fold increase upon treatment with interleukin-1{beta} or tumor necrosis factor {alpha}. In contrast, mRNA expression and proenzyme production of collagenase 1 were increased strongly, and to a similar extent, either by contact with 3-dimensional collagen or by proinflammatory cytokines. Conclusion. The expression of collagenase 3, in contrast to that of collagenase 1, is preferentially stimulated in synovial fibroblasts by 3-dimensional collagen rather than by proinflammatory cytokines. The induction of collagenase 3 by cell-matrix interactions represents a potential mechanism contributing to the invasive phenotype of synovial fibroblasts at sites of synovial invasion into cartilage in RA.
Keywords:	Cartilage, Cultured Cells, Collagen, Collagenases, Enzymologic Gene Expression Regulation, Fibroblasts, Gels, Immunocompromised Host, Immunohistochemistry, Inbred NOD Mice, In Situ Hybridization, Matrix Metalloproteinase 13, Messenger RNA, Rheumatoid Arthritis, SCID Mice, Synovial Membrane, Animals, Mice
Source:	Arthritis and Rheumatism
ISSN:	0004-3591
Publisher:	Wiley-Liss
Volume:	46
Number:	1
Page Range:	64-74
Date:	1 January 2002
Official Publication:	https://doi.org/10.1002/1529-0131(200201)46:1<64::AID-ART10069>3.0.CO;2-Q
PubMed:	View item in PubMed

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