title: Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice.
abstract: Growth arrest and DNA damage-inducible protein 45β (GADD45β) is expressed in normal and early osteoarthritic articular cartilage. We recently reported that GADD45β enhances CCAAT/enhancer binding protein β (C/EBPβ) activation in vitro. This study was undertaken in order to determine whether GADD45β is expressed with C/EBPβ in aging articular cartilage. We also investigated whether the synergistic expression of GADD45β and C/EBPβ may be involved in the mechanism of chondrocyte senescence. Senescence-accelerated mice (SAMP1) were used as a model of aging. GADD45β, C/EBPβ, and p21 were analyzed by immunohistochemistry. A luciferase reporter assay using ATDC5 cells was performed in order to examine p21 as a target gene of the GADD45β/C/EBPβ cascade. GADD45β exhibited increased expression in the aging articular cartilage of SAMP1 mice compared to that in control mice. The co-localization of GADD45β and C/EBPβ was confirmed by double immunostaining. The synergistic mechanisms of GADD45β and C/EBPβ on the gene regulation of p21, a molecule related to cellular senescence, were verified by a p21-luciferase reporter assay. Co-expression of C/EBPβ and p21 was confirmed. These observations suggest that the synergism between GADD45β and C/EBPβ may play an important role in cellular senescence in the aging articular cartilage.
authors.affiliation: Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shimada
authors.forename: Harutoshi
authors.initials: H
authors.lastname: Sakakima
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Tsuchimochi
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Matsuda
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.forename: Kosei
authors.initials: K
authors.lastname: Ijiri
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology*; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D004249:DNA Damage; D015971:Gene Expression Regulation, Enzymologic; D008156:Luciferases; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D010003:Osteoarthritis / Q000235:genetics / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D022782:CCAAT-Enhancer-Binding Protein-beta; D008156:Luciferases; D054462:p21-Activated Kinases; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins