Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

Hui Geng,Kutty Nandakumar,Rikard Holmdahl,Åke Oldberg,Stefan Carlsen,Ragnar Mattsson,Anders Aspberg

doi:10.1186/ar2551

Abstract

IntroductionCartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice.MethodsCOMP-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay.ResultsCOMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were similar in COMP-deficient and wild-type controls. COMP antibodies were not found in wild-type mice. Finally, COMP-deficient and wild-type mice responded similarly to collagen antibody-induced arthritis, indicating no difference in how collagen II antibodies interact with COMP-deficient cartilage during the initial stages of arthritis.ConclusionsCOMP deficiency enhances the early onset and development of chronic arthritis but does not affect collagen II autoimmunity. These findings accentuate the importance of COMP in cartilage stability.

Highlights

Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage
cartilage oligomeric matrix protein (COMP)-deficient and wild-type mice responded to collagen antibody-induced arthritis, indicating no difference in how collagen II antibodies interact with COMP-deficient cartilage during the initial stages of arthritis
It has been shown that the serum levels of cartilage oligomeric matrix protein (COMP) are elevated in a high proportion of patients suffering from Rheumatoid arthritis (RA) [3,4,5], which is of diagnostic interest and may indicate that this cartilage protein is involved in the disease process

Summary

Introduction

Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. We have investigated the development of CIA in COMP-deficient mice. Rheumatoid arthritis (RA) is a human autoimmune disease that affects the synovial membranes of the peripheral joints. It has been shown that the serum levels of cartilage oligomeric matrix protein (COMP) are elevated in a high proportion of patients suffering from RA [3,4,5], which is of diagnostic interest and may indicate that this cartilage protein is involved in the disease process. The CIA model shares some important features with RA, namely major histocompatibility complex (MHC) association and the fact that peripheral joints primarily are affected and that the disease can be divided into an acute

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Conclusion