In vitro response of osteoarthritic chondrocytes and fibroblast-like synoviocytes to 500-730 kDa hyaluronan amide derivative

The aim of this study was to compare the effects of native hyaluronan (HA) with that of its hexadecylamide derivative (HYADD) on proliferation of fibroblast-like synoviocytes (FLS) and chondrocytes. The production of inflammatory and anti-inflammatory cytokines was also analyzed in FLS cultures. The proliferation of osteoarthritis (OA) chondrocytes was enhanced when cells were treated with 0.5-1.5 mg/ml of HA or HYADD®4-G. This effect was completely suppressed by the anti-CD44 antibody. At 0.5 to 1 mg/ml, HA and HYADD®4-G did not influence the proliferation of normal or pathological FLS, however at the higher concentration (1.5 mg/ml), HYADD®4-G did significantly inhibit cell proliferation. As to effects on inflammation, a significant increase in the expression of the IL-10 gene was observed when FLS were pre-treated with TNF and then cultured in the presence of 0.5 mg/ml HYADD® 4-G or HA. The effects of HA derivatives on FLS proliferation and production of anti-inflammatory cytokines indicate that they may be of therapeutic benefit in osteoarthritis. The longer residence time in the joint cavity, the increased viscoelasticity and the anti-inflammatory potential of HYADD®4-G make it a better candidate than native HA for OA therapy.