title: Gene expression and localization of high-mobility group box chromosomal protein-1 (HMGB-1)in human osteoarthritic cartilage.
abstract: We investigated the expression and localization of high-mobility group box chromosomal protein-1 (HMGB-1) in human osteoarthritic (OA) cartilage in relation to the histopathological grade of cartilage destruction, and examined the role of HMGB-1 in the regulation of proinflammatory cytokine expression in chondrocytes. An immunohistochemical study demonstrated that total HMGB-1-positive cell ratios increase as the Osteoarthritis Research Society International (OARSI) histological grade increased. The population of cytoplasmic HMGB-1-positive chondrocytes was especially increased in the deep layers of higher-grade cartilage. The ratios and localization of receptors for advanced glycation end products (RAGE) expression by chondrocytes in Grade 2, 3, and 4 were significantly higher than those in Grade 1. In vitro stimulation with IL-1β, but not TNFα, significantly upregulated the expression of HMGB-1 mRNA by human OA chondrocytes. Both IL-1β and TNFα promoted the translocation of HMGB-1 from nuclei to cytoplasm. IL-1β and TNFα secretions were stimulated at higher levels of HMGB-1. The results of our study suggest the involvement of HMGB-1 in the pathogenesis of cartilage destruction in OA.
authors.affiliation: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Chuji
authors.initials: C
authors.lastname: Terada
authors.forename: Aki
authors.initials: A
authors.lastname: Yoshida
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nasu
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tomono
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hideo K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D024243:HMGB1 Protein; D053583:Interleukin-1beta; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha