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衰老关节软骨中软骨细胞的衰老：在加速衰老小鼠中，GADD45β 通过与 C/EBPβ 相关联来介导 p21 的表达。

Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice.

机构信息

Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.

出版信息

Pathol Res Pract. 2011 Apr 15;207(4):225-31. doi: 10.1016/j.prp.2011.01.007. Epub 2011 Feb 24.

DOI:10.1016/j.prp.2011.01.007
PMID:21353395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3427738/
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.

摘要

生长停滞和 DNA 损伤诱导蛋白 45β（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）的激活。进行这项研究是为了确定 GADD45β 是否与 C/EBPβ 在衰老的关节软骨中表达。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。使用加速老化小鼠（SAMP1）作为衰老的模型。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检测，以研究 p21 是否为 GADD45β/C/EBPβ 级联的靶基因。与对照组小鼠相比，SAMP1 小鼠衰老关节软骨中 GADD45β 的表达增加。通过双重免疫染色证实了 GADD45β 和 C/EBPβ 的共定位。通过 p21-荧光素酶报告基因检测验证了 GADD45β 和 C/EBPβ 对与细胞衰老相关的分子 p21 的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中的细胞衰老中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/7ea3cbc053f3/nihms-281706-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/f8abb2df54fc/nihms-281706-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/efb48df5d4e4/nihms-281706-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/a9233e07d70f/nihms-281706-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/7b46350a8cd0/nihms-281706-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/7ea3cbc053f3/nihms-281706-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/f8abb2df54fc/nihms-281706-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/efb48df5d4e4/nihms-281706-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/a9233e07d70f/nihms-281706-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/7b46350a8cd0/nihms-281706-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2b/3427738/7ea3cbc053f3/nihms-281706-f0005.jpg

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