Background/Purpose:

We evaluated the inflammatory effect of Coll2-1 peptide in osteoarthritic synoviocytes and rats by comparing peptide-induced inflammatory reaction with the one induced by bovine type II collagen or streptococcal cell wall.

Methods:

Human synoviocytes from knee OA patients (n=10) were pre-treated with AS0619 or CLI-095 (500nM, 1 and 2.5µM) before a 24 hours treatment with Coll2-1 peptide (¹⁰⁸HRGYPGLDG¹¹⁶; 0.45 or 4.5nmol). Expression of Interleukin (IL)-8, Vascular Endothelium Growth Factor (VEGF) and phosphorylation of the IkB-a and p65 were evaluated. Either Coll2-1 peptide, bovine type II collagen (CIA), streptococcal cell wall (SCW) or saline solution (100μl SC or 50μl IA) were injected into Lewis rats (n = 108). The Coll2-1 peptide was injected subcutaneously (SC; 20 and 200μg/100μl/animal) or intra-articular (IA; 0.5 and 5μg/50μl/animal). The bovine type II collagen was SC injected (200μg/100μl/animal), streptococcal cell wall in IA (5μg/50μl/animal). The animals were injected on day 10 and monitored for 21 or 28 days. Visual evaluation of the severity of arthritis and histological lesions were performed.

Results:

Coll2-1 at 0.45 nmol (**P<0.01) and 4.5 nmol (*P<0.05) significantly increased IL-8 gene expression and tended to increase VEGF expression by synoviocytes. With AS0619, a specific antiserum for Coll2-1 peptide, IL-8 expression significantly decreased (*P<0.05). Coll2-1 also induced both translocation of p65 and IkBa degradation. The latter being reduced with oxidative stress inhibitors. With CLI-095, we observed a decrease of IL-8 expression. In vivo, bovine type II collagen injection and Coll2-1 peptide injection resulted in an increase in visual arthritis score from D7. The global histological score was also increased by bovine type II collagen on D21 (p=0.0005) and on D28 (p<0.0001) and by the peptide Coll2-1 on D21 at the concentration of 200μg (p=0.0252) and on D28 at the concentration of 20μg (p=0.0025). Compared to control, all the components of the histological score were similarly modified by bovine type II collagen and the peptide Coll2-1 at both on D21 and on D28: increase in the inflammatory parameter (D21 200μg p=0.0217 and D28 20μg p=0.0021), reduction of proteoglycan contents (D28 200μg p=0.0072 and 20μg p=0.0024), increased cartilage degradation (J28 200μg p=0.0070 and 20μg p=0.0024) and modification of the subchondral bone (D21 200μg p=0.0025 and D28 20μg p=0.0065). Similarly, both the injection of SCW and that of Coll2-1 peptide induced an increase in the visual score from D10. The effect of Coll2-1 peptide on this score was identical to that of the SCW. Compared to control, SCW and Coll2-1 peptide increased the global histological score (D21 p=0.0119 and D28 p=0.0045). Like SCW, the injection of Coll2-1 peptide caused both inflammatory reaction, loss of proteoglycan, appearance of cartilage structural lesions (D28 0.5μg p=0.0201) and subchondral bone modification.

Conclusion:

Coll2-1 peptide is able to induce an inflammatory reaction and structural changes. Coll2-1 may initiate nonspecific natural immunity and therefore be a therapeutic target for biotherapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-coll2-1-peptide-of-collagen-type-ii-a-new-actor-of-synovitis-in-osteoarthritis/