RRC ID 18647
著者 Shimada H, Sakakima H, Tsuchimochi K, Matsuda F, Komiya S, Goldring MB, Ijiri K.
タイトル Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice.
ジャーナル Pathol Res Pract
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.
巻・号 207(4)
ページ 225-31
公開日 2011-4-15
DOI 10.1016/j.prp.2011.01.007
PII S0344-0338(11)00022-7
PMID 21353395
PMC PMC3427738
MeSH Aging / genetics Aging / metabolism* Animals Antigens, Differentiation / genetics Antigens, Differentiation / metabolism* CCAAT-Enhancer-Binding Protein-beta / genetics CCAAT-Enhancer-Binding Protein-beta / metabolism* Cartilage, Articular / cytology Cartilage, Articular / physiology* Cell Line Cellular Senescence / genetics Cellular Senescence / physiology Chondrocytes / cytology Chondrocytes / physiology* DNA Damage Gene Expression Regulation, Enzymologic Luciferases Male Mice Mice, Inbred C57BL Mice, Transgenic Models, Animal Osteoarthritis / genetics Osteoarthritis / physiopathology Promoter Regions, Genetic Signal Transduction p21-Activated Kinases / genetics* p21-Activated Kinases / metabolism
IF 2.05
引用数 14
WOS 分野 PATHOLOGY
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)