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) |