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Anin vitro model for studying mechanisms underlying synoviocyte-mediated cartilage invasion in rheumatoid arthritis

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Pathology & Oncology Research

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints involving the pathological development of an invasive and destructive pannus tissue which contributes to the loss of cartilage and bone. To further analyze the process of cartilage degradation and invasion, we have developed an in vitro model composed of cartilage matrix and synoviocytes (isolated from RA pannus tissue, as well as normal synovial membrane). The matrix is derived from pig articular cartilage and contains collagen type II and proteoglycans and is similar in composition to human cartilage. Data generated from this model reveal that synoviocytes isolated from RA pannus tissue invaded cartilage matrix in a manner which directly correlated with the severity of the disease. Analysis of mechanisms associated with the invasive process demonstrate that highly invasive RA synoviocytes maintain a round morphology during attachment and spreading on cartilage matrix, compared with their normal counterparts. Furthermore, the level of secretion of matrix metalloprote-inase (MMP) activity was shown to correlate with the RA phenotype, which could be modulated with a novel MMP inhibitor. Normal synoviocytes could be “converted” to an RA phenotype by specific inflammatory cytokines, such that invasion of cartilage matrix was augmented by cultunng these cells in the presence of 5 U/ml IL-lß or 18 U/ml TGFß. Invasion was inhibited by 150 U/ml TNFα, and unaffected by 100 ng/ml PDGF. In addition, synovial fluid from RA patients induced invasion of normal synoviocytes, in a concentration dependent manner, from 150% to 460%; however, synovial fluid from another inflammatory arthritidy (Crohn’s) did not augment invasion to the same degree. Moreover, this “converted effect” appears to be specific for synoviocytes, since similar effects could not be achieved with human skin fibroblasts. This in vitro model of synoviocyte-medi-ated cartilage invasion allows for further molecular characterization of the invasive properties of the synoviocyte which contribute to RA.

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Abbreviations

RA:

rhumatoid artharitis

TN:

Eα tumpor necrosis

factor-alpha:

TGFβ transforming growth factor beta

PDGF:

platelet derived growth factor. II-1βintereukin-I-beta

MMP:

matrix metalioprotemase

PBs:

phosphate buffered saline

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Arizona, Tucson

    Catherine A Frye

  2. Rheumatology, University of Arizona, Tucson

    David E Yocum

  3. Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia

    Rocky Tuan & Eiko Suyana

  4. Departments of Pediatrics and Internal Medicine, Saint Louis University, School of Medicine, St. Louis

    Elisabeth A Seftor, Richard EB Seftor, Zhila Khalkhaei Ellis, Terry L Moore & Mary JC Hendrix

  5. Department of Anatomy, University Iowa College of Medicine, Iowa City, USA

    Richard EB Seftor, Zhila Khalkhaei Ellis & Mary JC Hendrix

  6. Deparatment of Anatomy, College of Medicine, University of Iowa, 1569 Bowes; Science Bldg, 52242, Iowa City, IA

    Mary JC Hendrix

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  1. Catherine A Frye
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  2. David E Yocum
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A Frye, C., E Yocum, D., Tuan, R. et al. Anin vitro model for studying mechanisms underlying synoviocyte-mediated cartilage invasion in rheumatoid arthritis. Pathol. Oncol. Res. 2, 157–166 (1996). https://doi.org/10.1007/BF02903519

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  • DOI: https://doi.org/10.1007/BF02903519

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