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


METHODS
COMP-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.


RESULTS
COMP-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.


CONCLUSIONS
COMP 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.
Geng
Hui
H
Department of Experimental Medical Sciences, BMC, Lund University, Lund, Sweden. hui.geng@med.lu.se
Carlsen
Stefan
S
Nandakumar
Kutty Selva
KS
Holmdahl
Rikard
R
Aspberg
Anders
A
Oldberg
Ake
A
Mattsson
Ragnar
R
D017668:Age of Onset; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002358:Cartilage, Articular / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D024043:Collagen Type II / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008297:Male; D064235:Matrilin Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D051381:Rats; D012720:Severity of Illness Index
D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D018836:Inflammation Mediators; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins