title: Keratan sulfate suppresses cartilage damage and ameliorates inflammation in an experimental mice arthritis model.
abstract: Proteoglycans bearing keratan sulfate (KS), such as aggrecan, are components of the human cartilage extracellular matrix (ECM). However, the role of KS in influencing cartilage degradation associated with arthritis remains to be completely understood. KS side chains of the length found in human cartilage are not found in murine skeletal tissues. Using a murine model of inflammatory polyarthritis and cartilage explants exposed to interleukin-1α (IL-1α), we examined whether administering KS could influence intraarticular inflammation and cartilage degradation. Acute arthritis was induced by intravenous administration of an anti-type II collagen antibody cocktail, followed by an intraperitoneal injection of lipopolysaccharide. This treatment was followed by an intraperitoneal KS administration in half of the total mice to evaluate the therapeutic potential of KS for ameliorating arthritis. To investigate the therapeutic potential ex vivo, we examined cartilage fragility by measuring IL-1α-induced aggrecan release from cartilage explants treated with or without KS. Intraperitoneal KS administration ameliorated arthritis in DBA/1J mice. The aggrecan release induced by IL-1α was less in cartilage explants containing media with KS than in those without KS. Our data indicate that exogenous KS ameliorated arthritis in vivo and suppressed cartilage degradation ex vivo. KS may have important therapeutic potential in the treatment of inflammatory arthritis. The mechanism responsible for this requires further investigation, but KS may become a novel therapeutic agent for treating inflammatory diseases such as rheumatoid arthritis.
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. hayashimasatoshi@hotmail.com
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000097:blood; D007632:Keratan Sulfate / Q000502:physiology / Q000627:therapeutic use*; D008233:Lymphotoxin-alpha / Q000097:blood; D051379:Mice; D008811:Mice, Inbred DBA; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D020381:Interleukin-17; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D007632:Keratan Sulfate