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Open Access Research article

Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts

Mária Pásztói1, György Nagy2, Pál Géher2, Tamás Lakatos2, Kálmán Tóth3, Károly Wellinger3, Péter Pócza1, Bence György1, Marianna C Holub1, Ágnes Kittel4, Krisztina Pálóczy1, Mercédesz Mazán1, Péter Nyirkos1, András Falus15 and Edit I Buzas1*

Author Affiliations

1 Department of Genetics, Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest H-1089, Hungary

2 Department of Rheumatology, Semmelweis University, Frankel Leó utca 54, Budapest H-1027, Hungary

3 Department of Orthopedic Surgery, Szeged University, Semmelweis u.6, Szeged H-6725, Hungary

4 Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, Budapest H-1083, Hungary

5 Inflammation Biology and Immunogenomics Research Group, Hungarian Academy of Sciences-Semmelweis University, Nagyvárad tér 4, Budapest H-1089, Hungary

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Arthritis Research & Therapy 2009, 11:R68  doi:10.1186/ar2697

Published: 14 May 2009

Abstract

Introduction

Similar to matrix metalloproteinases, glycosidases also play a major role in cartilage degradation. Carbohydrate cleavage products, generated by these latter enzymes, are released from degrading cartilage during arthritis. Some of the cleavage products (such as hyaluronate oligosaccharides) have been shown to bind to Toll-like receptors and provide endogenous danger signals, while others (like N-acetyl glucosamine) are reported to have chondroprotective functions. In the current study for the first time we systematically investigated the expression of glycosidases within the joints.

Methods

Expressions of β-D-hexosaminidase, β-D-glucuronidase, hyaluronidase, sperm adhesion molecule 1 and klotho genes were measured in synovial fibroblasts and synovial membrane samples of patients with rheumatoid arthritis and osteoarthritis by real-time PCR. β-D-Glucuronidase, β-D-glucosaminidase and β-D-galactosaminidase activities were characterized using chromogenic or fluorogenic substrates. Synovial fibroblast-derived microvesicles were also tested for glycosidase activity.

Results

According to our data, β-D-hexosaminidase, β-D-glucuronidase, hyaluronidase, and klotho are expressed in the synovial membrane. Hexosaminidase is the major glycosidase expressed within the joints, and it is primarily produced by synovial fibroblasts. HexA subunit gene, one of the two genes encoding for the alpha or the beta chains of hexosaminidase, was characterized by the strongest gene expression. It was followed by the expression of HexB subunit gene and the β-D-glucuronidase gene, while the expression of hyaluronidase-1 gene and the klotho gene was rather low in both synovial fibroblasts and synovial membrane samples. Tumor growth factor-β1 profoundly downregulated glycosidase expression in both rheumatoid arthritis and osteoarthritis derived synovial fibroblasts. In addition, expression of cartilage-degrading glycosidases was moderately downregulated by proinflammatory cytokines including TNFα, IL-1β and IL-17.

Conclusions

According to our present data, glycosidases expressed by synovial membranes and synovial fibroblasts are under negative regulation by some locally expressed cytokines both in rheumatoid arthritis and osteoarthritis. This does not exclude the possibility that these enzymes may contribute significantly to cartilage degradation in both joint diseases if acting in collaboration with the differentially upregulated proteases to deplete cartilage in glycosaminoglycans.