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Local expression of matrix metalloproteinases, cathepsins, and their inhibitors during the development of murine antigen-induced arthritis.

Schurigt U, Stopfel N, Hückel M, Pfirschke C, Wiederanders B, Bräuer R - Arthritis Res. Ther. (2004)

Bottom Line: Proteoglycan loss analysed by safranin O staining was also strongest on days 1 and 3.Expression of most of the proteinases followed the expression of pro-inflammatory cytokines.The present study indicates that MMPs and cathepsins are important in AIA and contribute to the degradation of cartilage and bone.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Pathology, Friedrich Schiller University, Jena, Germany. Uta.Schurigt@med.uni-jena.de

ABSTRACT
Cartilage and bone degradation, observed in human rheumatoid arthritis (RA), are caused by aberrant expression of proteinases, resulting in an imbalance of these degrading enzymes and their inhibitors. However, the role of the individual proteinases in the pathogenesis of degradation is not yet completely understood. Murine antigen-induced arthritis (AIA) is a well-established animal model of RA. We investigated the time profiles of expression of matrix metalloproteinase (MMP), cathepsins, tissue inhibitors of matrix metalloproteinases (TIMP) and cystatins in AIA. For primary screening, we revealed the expression profile with Affymetrix oligonucleotide chips. Real-time polymerase chain reaction (PCR) analyses were performed for the validation of array results, for tests of more RNA samples and for the completion of the time profile. For the analyses at the protein level, we used an MMP fluorescence activity assay and zymography. By a combination of oligonucleotide chips, real-time PCR and zymography, we showed differential expressions of several MMPs, cathepsins and proteinase inhibitors in the course of AIA. The strongest dysregulation was observed on days 1 and 3 in the acute phase. Proteoglycan loss analysed by safranin O staining was also strongest on days 1 and 3. Expression of most of the proteinases followed the expression of pro-inflammatory cytokines. TIMP-3 showed an expression profile similar to that of anti-inflammatory interleukin-4. The present study indicates that MMPs and cathepsins are important in AIA and contribute to the degradation of cartilage and bone.

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Proteoglycan (PG) degradation in articular cartilage between femur and patella. Sections were stained with safranin O and counterstained with hematoxylin (see Materials and Methods) to determine the proteoglycan contents in murine knee joints before and after the induction of antigen-induced arthritis (AIA). Proteoglycans in cartilage were stained red by safranin O. The proteoglycan content in sections before and after arthritis induction reflects the cartilage degradation during the development of AIA. A, articular cartilage; F, femur; I, infiltrate; P, patella. The proteoglycan content in articular cartilage was decreased on days 1 and 3 in comparison with control day 0 animals. Original magnification × 100.
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Figure 7: Proteoglycan (PG) degradation in articular cartilage between femur and patella. Sections were stained with safranin O and counterstained with hematoxylin (see Materials and Methods) to determine the proteoglycan contents in murine knee joints before and after the induction of antigen-induced arthritis (AIA). Proteoglycans in cartilage were stained red by safranin O. The proteoglycan content in sections before and after arthritis induction reflects the cartilage degradation during the development of AIA. A, articular cartilage; F, femur; I, infiltrate; P, patella. The proteoglycan content in articular cartilage was decreased on days 1 and 3 in comparison with control day 0 animals. Original magnification × 100.

Mentions: Safranin O staining reflects the proteoglycan content of cartilage. Proteoglycan loss is an early marker of cartilage destruction. The staining intensity of proteoglycans was very weak during the acute stage of AIA on days 1 and 3, corresponding to the days of highest proteinase expression, in comparison with control joints on day 0 (Fig. 7).


Local expression of matrix metalloproteinases, cathepsins, and their inhibitors during the development of murine antigen-induced arthritis.

Schurigt U, Stopfel N, Hückel M, Pfirschke C, Wiederanders B, Bräuer R - Arthritis Res. Ther. (2004)

Proteoglycan (PG) degradation in articular cartilage between femur and patella. Sections were stained with safranin O and counterstained with hematoxylin (see Materials and Methods) to determine the proteoglycan contents in murine knee joints before and after the induction of antigen-induced arthritis (AIA). Proteoglycans in cartilage were stained red by safranin O. The proteoglycan content in sections before and after arthritis induction reflects the cartilage degradation during the development of AIA. A, articular cartilage; F, femur; I, infiltrate; P, patella. The proteoglycan content in articular cartilage was decreased on days 1 and 3 in comparison with control day 0 animals. Original magnification × 100.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1064893&req=5

Figure 7: Proteoglycan (PG) degradation in articular cartilage between femur and patella. Sections were stained with safranin O and counterstained with hematoxylin (see Materials and Methods) to determine the proteoglycan contents in murine knee joints before and after the induction of antigen-induced arthritis (AIA). Proteoglycans in cartilage were stained red by safranin O. The proteoglycan content in sections before and after arthritis induction reflects the cartilage degradation during the development of AIA. A, articular cartilage; F, femur; I, infiltrate; P, patella. The proteoglycan content in articular cartilage was decreased on days 1 and 3 in comparison with control day 0 animals. Original magnification × 100.
Mentions: Safranin O staining reflects the proteoglycan content of cartilage. Proteoglycan loss is an early marker of cartilage destruction. The staining intensity of proteoglycans was very weak during the acute stage of AIA on days 1 and 3, corresponding to the days of highest proteinase expression, in comparison with control joints on day 0 (Fig. 7).

Bottom Line: Proteoglycan loss analysed by safranin O staining was also strongest on days 1 and 3.Expression of most of the proteinases followed the expression of pro-inflammatory cytokines.The present study indicates that MMPs and cathepsins are important in AIA and contribute to the degradation of cartilage and bone.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Pathology, Friedrich Schiller University, Jena, Germany. Uta.Schurigt@med.uni-jena.de

ABSTRACT
Cartilage and bone degradation, observed in human rheumatoid arthritis (RA), are caused by aberrant expression of proteinases, resulting in an imbalance of these degrading enzymes and their inhibitors. However, the role of the individual proteinases in the pathogenesis of degradation is not yet completely understood. Murine antigen-induced arthritis (AIA) is a well-established animal model of RA. We investigated the time profiles of expression of matrix metalloproteinase (MMP), cathepsins, tissue inhibitors of matrix metalloproteinases (TIMP) and cystatins in AIA. For primary screening, we revealed the expression profile with Affymetrix oligonucleotide chips. Real-time polymerase chain reaction (PCR) analyses were performed for the validation of array results, for tests of more RNA samples and for the completion of the time profile. For the analyses at the protein level, we used an MMP fluorescence activity assay and zymography. By a combination of oligonucleotide chips, real-time PCR and zymography, we showed differential expressions of several MMPs, cathepsins and proteinase inhibitors in the course of AIA. The strongest dysregulation was observed on days 1 and 3 in the acute phase. Proteoglycan loss analysed by safranin O staining was also strongest on days 1 and 3. Expression of most of the proteinases followed the expression of pro-inflammatory cytokines. TIMP-3 showed an expression profile similar to that of anti-inflammatory interleukin-4. The present study indicates that MMPs and cathepsins are important in AIA and contribute to the degradation of cartilage and bone.

Show MeSH
Related in: MedlinePlus