Histone deacetylase1 promotes TGF-β1-mediated early chondrogenesis through down-regulating canonical Wnt signaling
Histone deacetylase1 promotes TGF-β1-mediated early chondrogenesis through down-regulating canonical Wnt signaling
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DOI：
10.1016/j.bbrc.2014.10.021
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发表时间：
2014-10-31
影响因子：
3.1
通讯作者：
Zhang, Xiaoling
中科院分区：
文献类型：
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作者：
Huang, Xiaoju;Xu, Jiajia;Zhang, Xiaoling
在胚胎发育和骨修复过程中的软骨形成都涉及间充质干细胞（MSCs）的分化。Wnt/β-连环蛋白信号通路抑制早期软骨形成，并在转化生长因子-β 1（TGF-β 1）诱导的软骨形成过程中下调。然而，参与该过程的调节分子是未知的。本研究旨在探讨软骨形成过程中Wnt/β-catenin通路下调的机制。将TGF-β 1诱导的C3 H10 T1/2微团培养物用作软骨细胞分化模型。实时荧光定量PCR检测基因表达谱。通过荧光素酶分析、染色质免疫沉淀（ChIP）分析、免疫共沉淀（CoIP）分析和体外泛素化分析研究HDAC 1对β-catenin的调节作用。在这项研究中，我们发现HDAC 1通过直接结合其启动子来诱导和抑制β-连环蛋白基因表达。此外，HDAC 1还可以通过其脱乙酰基酶结构域与脱乙酰化的β-catenin蛋白相互作用，导致β-catenin蛋白降解。我们的研究结果表明，HDAC 1在软骨形成中起着重要作用，并可能代表一个治疗靶点，用于调节软骨发育。(C)2014爱思唯尔公司All rights reserved.
Cartilage formation during both embryonic development and bone repairing processes involves mesenchymal stem cells (MSCs) differentiation. Wnt/beta-catenin signaling pathway inhibits early chondrogenesis and is down-regulated during Transforming growth factor-beta 1 (TGF-beta 1)-induced chondrogenesis. However, the regulatory molecules that participate in the process is unknown. This study was designed to investigate the underlying mechanisms that down-regulate Wnt/beta-catenin pathway during chondrogenesis. TGF-beta 1-induced micromass cultures of C3H10T1/2 were used as chondrocyte differentiation model. Gene expression profile was detected by realtime-PCR. Regulatory role of HDAC1 on beta-catenin was investigated by luciferase assay, chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation (CoIP) assay and in vitro ubiquitination assay. In this study, we showed that HDAC1 was induced and suppressed beta-catenin gene expression through direct binding to its promoter. Besides, HDAC1 could also interact with deacetylate beta-catenin protein through its deacetylase domain, which causes degradation of beta-catenin. Our results indicate that HDAC1 plays an important role in chondrogenesis and may represent a therapeutic target for modulation of cartilage development. (C) 2014 Elsevier Inc. All rights reserved.