Serum COMP in Animal Disease Models |
Focus letter 3, 2009 |
A decrease in serum COMP concentration is a useful surrogate marker to verify a chondroprotective effect of new anti-arthritic drugs in animal models[1] |
In a recent study, using AnaMar’s Animal COMP test, Ferrándiz et al [1]. could show a chondroprotective effect of a CO-releasing molecule (CORM-3) in collagen-induced arthritis in mice by measuring a decrease in serum COMP. This decrease in serum COMP was associated with less apparent cartilage erosions in histological measurements. This is not the first publication using serum COMP with this aim. It has been used in several earlier animal studies coming to similar conclusions when anti-arthritic substances were used
In two early studies [7-8], focused on the erosive arthritis per se in animal models, a high correlation was shown between the serum COMP level and the arthritis score. Furthermore, animals with high COMP levels showed a chronic disease course6 and peaked later in the disease [6-7] not associated with early markers of systemic inflammation [7]. |
REFERENCES 1. Ferrándiz ML et al: Ann Rheum Dis 2008, 67: 1211-1217 2. Larsson E et al: Ann Rheum Dis 2005, 64: 494-496 3. Larsson E et al : Rheumatology 2004, 43: 428-434 4. Joosten LAB et al: Arthritis Res 1999, 1: 81-91 5. Joosten LAB et al : J Immun 1999, 163: 5049-5055 6. Larsson E et al: Br. J Rheumatol 1997, 36: 1258-1261 7. Larsson E et al: Rheumatology 2002, 41: 996-1000 8. Vingsbo-Lundberg C et al: Arthritis Rheum 1998, 41: 544-550
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Serum COMP could be used to verify a chondroprotective effect of a new class of anti-inflammatory agents (CO-releasing molecules) |
The aim of the study was to investigate if the CO-releasing molecule 3 (CORM-3), belonging to a novel class of anti-inflammatory agents, modifies the progression of collagen-induced arthritis in DBA-1/J mice. The arthritic mice showed severe histological changes and significantly increased serum levels of COMP. Serum COMP concentrations were significantly lower and the histological pattern less apparent in mice treated with CORM-3 from days 22-31. The anti-inflammatory effect was also documented by using several other inflammatory markers. This study proved, in agreement with earlier studies, that serum COMP is increased in animal models with destructive arthritis and reflects the severity of the destructive process in the joint. |
Ferrándiz, ML.; Maicas, N; Garcia-Armandis, I.; Terencio, MC.; Motterlini, R.; Devesa, I.; Joosten, LAB.; van den Berg, WB.; Alcaraz, MJ:
Treatment with a CO-releasing molecule (CORM-3) reduces joint inflammation and erosion in murine collagen-induced arthritis.
Ann Rheum Dis 2008, 67: 1211-1217 |
Serum COMP concentration was used to verify the chondroprotective effect of an inhibitor (CNI-1493) of pro-inflammatory cytokine production |
| The aim of the study was to investigate the effect of CNI-1493, a known inhibitor of pro-inflammatory cytokine production, on the development of collagen-induced arthritis in rats. Based on an earlier study of this animal disease model they used serum COMP as a marker of cartilage destruction. The serum COMP was significantly higher in the non-treated group and decreased significantly over time in the CNI-1493 treated group. The authors conclude, as in the earlier study, that the protective effect against cartilage destruction can be monitored by measuring serum COMP quantitatively. |
Larsson, E.; Harris, HE.; Palmblad, K.; Månsson, B.; Saxne, T.; Klareskog, L.: CNI-1 493 an inhibitor of pro inflammatory cytokines, retards cartilage destruction in rats with collagen induced arthritis.
Ann Rheum Dis. 2005, 64: 494-496 |
The cartilage-protective effect of corticosteroids was immediately mirrored by a decrease in serum COMP values in rat collagen arthritis |
| The aim of this study was to investigate if the serum COMP levels correlate with the cartilage destruction in collagen-induced arthritis in rats. There was a highly significant correlation (r=0.77, p<0.001) between serum COMP concentration and the extent of cartilage destruction at day 25 after induction of the arthritis. Corticosteroid-treated animals showed a lower final cartilage score and no further increase in serum COMP. The authors conclude that the cartilage-protective effect of corticosteroids was immediately mirrored by a decrease in serum COMP values. |
| Larsson, E.; Erlandsson, Harris, H.; Larsson, A; Månsson, B.; Saxne, T.; Klareskog, L.:
Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP.
Rheumatology 2004, 43:428-434 |
Systemic high dose of IL-4 has a chondroprotective effect on collagen-induced arthritis as measured by a decrease in serum COMP level and cartilage pathology |
| The aim of the study was to investigate the chondroprotective effect by systemic high dose IL-4 therapy on established collagen-induced arthritis in mice. A decrease in serum COMP was obtained in treated animals accompanied by reduced cartilage pathology. A low dose of prednisolone together with IL-4 had a synergistic effect on serum COMP reduction and inflammatory parameters. |
Joosten, LAB-; Lubberts, E.; Helsen, MMA.; Saxne, T.; Coenen-de Roo, ChJJ.; Heinegård, D.; van den Berg, WB. :
Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine typ II collagen-induced arthritis.
Arthritis Res 1999, 1:81-91 |
Changes in serum COMP concentration primarily reflect the destructive process in joint cartilage and not the inflammation per se |
| The aim of the study was to investigate the difference of TNF-α and IL-1 on cartilage and bone destruction in collagen-induced arthritis of mice. Neutralization of IL-1, but not TNF-a, was associated with normalization of serum COMP concentration and less pronounced cartilage and bone destruction. The results indicate that changes in serum COMP concentration primarily reflects processes in the cartilage and not the inflammation per se. |
Joosten, LAB.; Helsen, MMA.; Saxne, T.; van de Lo, FAJ.; Heinegård, D.; van den Berg, WB;.:
IL-αß blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-α blockade only ameliorates joint inflammation.
J Immun 1999, 163:5049-5055 |
Serum COMP can be used as a non-invasive tool to monitor cartilage involvement in experimental arthritis |
| This is the first study investigating the possibility to use serum COMP as a marker of cartilage destruction in animal model of arthritis. Increased levels of serum COMP was shown from day 21 and increased further to the end of the experiment at day 28. The increase was associated to clinical joint score and pathology of cartilage and bone destruction. The authors conclude that serum COMP can be used as a non-invasive tool to monitor cartilage involvement in experimental arthritis. |
Larsson, E.; Musser, A.; Heinegård, D.; Klareskog, L.; Saxne, T.:
Increased serum levels of cartilage oligomeric matrix protein and bone sialoprotein in rats with collagen arthritis.
Br J Rheumatol 1997, 36:1258-1261 |
Serum COMP reflects the cartilage destructive process as disclosed by using different animal disease models and markers of inflammation |
| The aim of this study was to investigate if serum COMP could be used as a biomarker to detect the cartilage destruction in collagen-induced and oil-induced arthritis in rats. Fibrinogen was used as a marker of systemic inflammation. Fibrinogen increased early and before the peak of the arthritis score whereas serum COMP increased after the onset of the arthritis and peaked later in the disease. Serum COMP level was significantly higher in the more destructive collagen-induced arthritis compared to the less destructive oil-induced arthritis. The authors conclude that serum COMP reflects the cartilage destruction process and not the inflammation. |
| Larsson, E.; Erlandsson, Harris H.; Lorentzen, JC.; Larssson, A.; Månsson, B.; Klareskog, L.; Saxne, T. :
Serum concentrations of cartilage oligomeric matrix protein, fibrinogen and hyaluronan distinguish inflammation and cartilage destruction in experimental arthritis in rats.
Rheumatology 2002, 41:996-1000
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High serum COMP is associated to the severity of experimental arthritis and indicates a chronic course of the disease |
| The aim of this study was to evaluate serum COMP as a new, recently published, biomarker to monitor cartilage destruction in experimental arthritis. Serum COMP was measured in three diff erent rat breeds (DA, E3 and DAxE3) with pristine-induced arthritis. The serum COMP level showed a high correlation to macroscopical arthritis (r>0.9). Furthermore, an important finding was that rats with a chronic disease course had a significantly (p<0.01) higher concentration of serum COMP in the acute stage than rats with remitting disease. This indicates the possibility to use the serum COMP level for clinical prediction. |
Vingsbo-Lundberg, C.; Saxne, T.; Olsson, H.; Holmdahl, R.:
Increased serum levels of cartilage oligomeric matrix protein in chronic erosive arthritis in rats.
Arthritis Rheum 1998, 41:544-550 |
