The role of collagen breakdown products inosteoarthritis

The mechanism by which collagen breakdown products play a role in the pathogenesis of Osteoarthritis is unknown. However, the collagen degradation product proline-glycine-proline (PGP), which is homologous to key sequences of CXCL8, stimulates the CXCR1 and CXCR2 receptors and prolongs the influx of neutrophils. The present study was conducted to examine the effect of collagen breakdown products on bovine chondrocytes. Chondrocytes and explants were obtained from bovine articular cartilage slices. Isolated chondrocytes were treated with CXCL8 or PGP and/or glycine-proline-proline (GPP) to assess their potential to produce nitric oxide (NO). The effect of collagen fragments on the rate of proteoglycan release was determined in explants. RT-PCR was used to obtain the expression of the CXCR1-receptor and the hypertrophic marker matrix metalloproteinase-13 (MMP-13) in control and CXCL8-stimulated chondrocytes. Our data show that combination of PGP with GPP causes a dose-dependent increase in proteoglycan release from explants. Furthermore, a small increase was observed in the NO production in explants stimulated with PGP. After 5 days incubation without stimulation or in the presence of CXCL8, the CXCR1 gene expression was down regulated in chondrocytes. Finally, both CXCL8 increased MMP-13 expression in chondrocytes. Collectively our data show that collagen products are able to induce activation of the chondrocyte, but further investigations are needed to clarify the way of action.