SAT0052 The coll2–1 peptide of collagen type ii: a new actor of synovitis in osteoarthritis
Authors: C. Lambert, D. Borderie, F. Rannou, Y. Henrotin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) is characterised by degradation of the extracellular matrix associated with inadequate repair responses including pro-inflammatory pathways of nonspecific natural immune response. <h3>Objectives</h3> 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. <h3>Methods</h3> Human synoviocytes from knee OA patients (n=10) were pre-treated with AS0619 or CLI-095 (500 nM, 1 and 2.5 µM) before a 24 hours treatment with Coll2–1 peptide (<sup>108</sup>HRGYPGLDG<sup>116</sup>; 0.45 or 4.5 nmol). Expression of Interleukin (IL)−8, Vascular Endothelium Growth Factor (VEGF) and phosphorylation of the IkB-α and p65 were evaluated. Either Coll2–1 peptide, bovine type II collagen (CIA), streptococcal cell wall (SCW) or saline solution (100 µl SC or 50 µl IA) were injected into Lewis rats (n=108). The Coll2–1 peptide was subcutaneously injected (SC; 20 and 200 µg/100 µl/animal) or intra-articular (IA; 0.5 and 5 µg/50 µl/animal). The bovine type II collagen was SC injected (200 µg/100 µl/animal), streptococcal cell wall in IA (5 µg/50 µl/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. <h3>Results</h3> Coll2–1 at 0.45 nmol (**p&lt;0.01) and 4.5 nmol (*p&lt;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&lt;0.05). Coll2–1 also induced both translocation of p65 and IkB-α degradation. The latter being reduced with oxidative stress inhibitors. With CLI-095, we observed a decrease of IL-8 expression. <i>In vivo</i>, 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&lt;0.0001) and by the peptide Coll2–1 on D21 at the concentration of 200 µg (p=0.0252) and on D28 at the concentration of 20 µg (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 200 µg p=0.0217 and D28 20 µg p=0.0021), reduction of proteoglycan contents (D28 200 µg p=0.0072 and 20 µg p=0.0024), increased cartilage degradation (J28 200 µg p=0.0070 and 20 µg p=0.0024) and modification of the subchondral bone (D21 200 µg p=0.0025 and D28 20 µg 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 0.5 µg p=0.0201) and subchondral bone modification. <h3>Conclusions</h3> Coll2–1 peptide is able to induce an inflammatory reaction and structural changes in articular cartilage and subchondral bone comparable to those induced by SCW and bovine type II collagen. In conclusion, Coll2–1 may initiate nonspecific natural immunity and therefore be a therapeutic target for biotherapy. <h3>Disclosure of Interest</h3> None declared