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Comparative Study
. 2005;7(4):R852-61.
doi: 10.1186/ar1756. Epub 2005 May 12.

Regional assessment of articular cartilage gene expression and small proteoglycan metabolism in an animal model of osteoarthritis

Allan A Young  1 , Margaret M Smith, Susan M Smith, Martin A Cake, Peter Ghosh, Richard A Read, James Melrose, David H Sonnabend, Peter J Roughley, Christopher B Little
Affiliations
Comparative Study

Regional assessment of articular cartilage gene expression and small proteoglycan metabolism in an animal model of osteoarthritis

Allan A Young et al. Arthritis Res Ther. 2005.

Abstract

Osteoarthritis (OA), the commonest form of arthritis and a major cause of morbidity, is characterized by progressive degeneration of the articular cartilage. Along with increased production and activation of degradative enzymes, altered synthesis of cartilage matrix molecules and growth factors by resident chondrocytes is believed to play a central role in this pathological process. We used an ovine meniscectomy model of OA to evaluate changes in chondrocyte expression of types I, II and III collagen; aggrecan; the small leucine-rich proteoglycans (SLRPs) biglycan, decorin, lumican and fibromodulin; transforming growth factor-beta; and connective tissue growth factor. Changes were evaluated separately in the medial and lateral tibial plateaux, and were confirmed for selected molecules using immunohistochemistry and Western blotting. Significant changes in mRNA levels were confined to the lateral compartment, where active cartilage degeneration was observed. In this region there was significant upregulation in expession of types I, II and III collagen, aggrecan, biglycan and lumican, concomitant with downregulation of decorin and connective tissue growth factor. The increases in type I and III collagen mRNA were accompanied by increased immunostaining for these proteins in cartilage. The upregulated lumican expression in degenerative cartilage was associated with increased lumican core protein deficient in keratan sulphate side-chains. Furthermore, there was evidence of significant fragmentation of SLRPs in both normal and arthritic tissue, with specific catabolites of biglycan and fibromodulin identified only in the cartilage from meniscectomized joints. This study highlights the focal nature of the degenerative changes that occur in OA cartilage and suggests that altered synthesis and proteolysis of SLRPs may play an important role in cartilage destruction in arthritis.

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Figures

Figure 1
Figure 1
Histology. Representative histology of medial (a, b) and (c–f) lateral tibial plateau cartilage from nonoperated control (panels a and c) and meniscectomized (panels b and d-f) ovine stifle joints. Cell cloning is a prominent feature in the lateral tibial plateau following meniscectomy (asterisk). Osteophyte formation is evident at the lateral joint margin (panel f, arrowheads), and the area of most severe cartilage damage with surface fibrillation (rectangle, panel e) and the adjacent area (circle, panel d) are indicated. Toluidine blue-fast green stain. Scale bar: 250 μm.
Figure 2
Figure 2
Immunolocalisation. Immunolocalization of types I (a–d), II (e–h) and III (I–l) collagens in medial (panels a, b, e, f, I and j) and lateral (panels c, d, g, h, k and l) tibial plateau cartilage. Sections from representative nonoperated control (panels a, c, e, g, I and k) and meniscectomized (b, d, f, h, j and l) joints are shown. Scale bar: 250 μm.
Figure 3
Figure 3
Changes in mRNA levels. Changes in (a) lateral tibial plateau (LTP) and (b) medial tibial plateau (MTP) cartilage mRNA levels of aggrecan, type I, II, and III collagen, decorin, biglycan, fibromodulin, lumican, transforming growth factor (TGF)-β and connective tissue growth factor (CTGF) following lateral meniscectomy (MEN) relative to nonoperated control (NOC) values. Values are expressed as mean ± standard deviation. There were three samples for the NOC MTP, six for the NOC LTP, five for the MEN MTP and six for the MEN LTP groups. *P < 0.05, **P < 0.01.
Figure 4
Figure 4
Western blot. Western blot analysis of decorin, biglycan, fibromodulin and lumican in extracts of human osteoarthritis cartilage (OA), nonoperated control (NOC) and lateral meniscectomized (MEN) ovine cartilage samples. Core protein fragments of decorin and fibromodulin that were only identified in MEN are marked with an asterisk. Equivalent amounts of extract from equal dry weights of tissue were loaded per lane following treatment with chondroitinase ABC (ChABC). Additionally, Western blot analysis of lumican was performed following treatment with ChABC, endo-β-galactosidase (EBG) and keratanase II (KII). The migration positions of prestained protein standards are indicated on the left.
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References

    1. Maroudas AI. Balance between swelling pressure and collagen tension in normal and degenerate cartilage. Nature. 1976;260:808–809. - PubMed
    1. Iozzo RV. The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem. 1999;274:18843–18846. doi: 10.1074/jbc.274.27.18843. - DOI - PubMed
    1. Svensson L, Oldberg A, Heinegard D. Collagen binding proteins. Osteoarthritis Cartilage. 2001;9:S23–S28. doi: 10.1053/joca.2001.0440. - DOI - PubMed
    1. Schonherr E, Hausser H, Beavan L, Kresse H. Decorin-type I collagen interaction. Presence of separate core protein-binding domains. J Biol Chem. 1995;270:8877–8883. doi: 10.1074/jbc.270.15.8877. - DOI - PubMed
    1. Hedbom E, Heinegard D. Binding of fibromodulin and decorin to separate sites on fibrillar collagens. J Biol Chem. 1993;268:27307–27312. - PubMed

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