| Decorin (DCN) is a small, leucine-rich, extracellular matrix proteoglycan that binds collagen. We tested the hypothesis that DCN binding to collagen inhibits phagocytosis of collagen fibrils. Experimentally, this was achieved by analyzing the phagocytosis of collagen and DCN/collagen-coated fluorescent beads by Rat-2 and gingival fibroblasts. The binding and internalization of DCN/collagen-coated beads decreased dose-dependently with increasing concentrations of DCN (p<0.001). DCN-mediated inhibition of collagen phagocytosis was attributed to DCN-collagen interactions. A mimetic peptide corresponding to the leucine-rich repeat (LRR) 3 bound to a triple helical peptide containing the alpha2 integrin-binding site of collagen. When collagen beads were co-incubated with this peptide and a mimetic peptide for LRR 4, marked inhibition (∼55%) of collagen phagocytosis was observed. Thus, the DCN-mediated inhibition of collagen phagocytosis can be attributed to a novel collagen binding domain in DCN which acts co-operatively with LRR 4 to mask the alpha2beta1 integrin-binding site on collagen. |
