title: Keratan sulfate and related murine glycosylation can suppress murine cartilage damage in vitro and in vivo.
abstract: Keratan sulfate (KS) proteoglycan side chains are abundant in the human cartilage matrix, but these chains have been said to be absent in murine skeletal tissues. We previously showed that KS suppresses cartilage damage and ameliorates inflammation in mice arthritis model. Because mice deficient of N-acetylglucosamine 6-O-sulfotransferase-1 (GlcNAc6ST-1) (KS biosynthesis enzyme) are now available, we decided to do further examinations. We examined, in culture, the difference between GlcNAc6ST-1(-/-) and wild-type (WT) mice for interleukin (IL)-1α-induced glycosaminoglycan (GAG) release from the articular cartilage. Arthritis was induced by intravenous administration of an anti-type II collagen antibody cocktail and subsequent intraperitoneal injection of lipopolysaccharide. We examined the differences in arthritis severities in the two genotypes. After intraperitoneal KS administration in phosphate-buffered saline (PBS) or PBS alone, we evaluated the potential of KS in ameliorating arthritis and protecting against cartilage damage in deficient mice. GAG release induced by IL-1α in the explants, and severity of arthritis were greater in GlcNAc6ST-1(-/-) mice than their WT littermates. Intraperitoneal KS administration effectively suppressed arthritis induction in GlcNAc6ST-1(-/-) mice. Thus, GlcNAc6ST-1(-/-) mice cartilage is more fragile than WT mice cartilage, and exogenous KS can suppress arthritis induction in GlcNAc6ST-1(-/-) mice. Vestigial KS chain or altered glycosylation in articular cartilage in GlcNAc6ST-1(-/-) mice may be protective against arthritis and associated cartilage damage as well as cartilage damage in culture. KS may offer therapeutic opportunities for chondroprotection and suppression of joint damage in inflammatory arthritis and may become a therapeutic agent for treating 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: Toshihisa
authors.initials: T
authors.lastname: Kojima
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D006031:Glycosylation; D007632:Keratan Sulfate / Q000008:administration & dosage* / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008811:Mice, Inbred DBA; D015238:Sulfotransferases / Q000235:genetics; D000097811:Carbohydrate Sulfotransferases
chemical_list: D007632:Keratan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases