Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice.
Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice.
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DOI：
10.1016/j.prp.2011.01.007
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发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Ijiri K
中科院分区：
文献类型：
--
作者：
Shimada H;Sakakima H;Tsuchimochi K;Matsuda F;Komiya S;Goldring MB;Ijiri K
生长停滞和 DNA 损伤诱导蛋白 45 β (GADD45β) 在正常和早期骨关节炎关节软骨中表达。我们最近报道 GADD45β 在体外增强 CCAAT/增强子结合蛋白 β (C/EBPβ) 激活。进行本研究的目的是确定 GADD45β 是否在老化的关节软骨中与 C/EBPβ 一起表达。我们还研究了GADD45β和C/EBPβ的协同表达是否可能参与软骨细胞衰老的机制。衰老加速小鼠（SAMP1）被用作衰老模型。通过免疫组织化学分析 GADD45β、C/EBPβ 和 p21。使用 ATDC5 细胞进行荧光素酶报告基因测定，以检查 p21 作为 GADD45β/C/EBPβ 级联的靶基因。与对照小鼠相比，GADD45β 在 SAMP1 小鼠衰老的关节软骨中表现出表达增加。通过双重免疫染色证实了 GADD45β 和 C/EBPβ 的共定位。通过 p21-荧光素酶报告基因测定验证了 GADD45β 和 C/EBPβ 对细胞衰老相关分子 p21 基因调控的协同机制。证实了 C/EBPβ 和 p21 的共表达。这些观察结果表明，GADD45β 和 C/EBPβ 之间的协同作用可能在衰老关节软骨的细胞衰老中发挥重要作用。
Growth arrest and DNA damage-inducible protein 45 β (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.
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影响因子：
4.8
作者：
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