title: In vitro response of osteoarthritic chondrocytes and fibroblast-like synoviocytes to a 500-730 kDa hyaluronan amide derivative.
abstract: 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(-1) of HA or HYADD®4-G. This effect was completely suppressed by the anti-CD44 antibody. At 0.5 to 1 mg mL(-1) , HA and HYADD®4-G did not influence the proliferation of normal or pathological FLS; however, at the higher concentration (1.5 mg mL(-1) ), 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 pretreated with tumor necrosis factor alpha and then cultured in the presence of 0.5 mg mL(-1) 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 OA. 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.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Italy. paola.brun@unipd.it
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Barbara
authors.initials: B
authors.lastname: Zavan
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vindigni
authors.forename: Antonella
authors.initials: A
authors.lastname: Schiavinato
authors.forename: Assunta
authors.initials: A
authors.lastname: Pozzuoli
authors.forename: Claudio
authors.initials: C
authors.lastname: Iacobellis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abatangelo
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: D016207:Cytokines; D006820:Hyaluronic Acid