Histone deacetylase1 promotes TGF-β1-mediated early chondrogenesis through down-regulating canonical Wnt signaling

• Published in: Biochemical and biophysical research communications 2014-10, Vol.453 (4), p.810-816
• Main Authors: Huang, Xiaoju, Xu, Jiajia, Huang, Mingjian, Li, Jiao, Dai, Liming, Dai, Kerong, Zhang, Xiaoling
• Format: Article
• Language: English
• Subjects: beta Catenin - metabolism; Chondrocytes - cytology; Chondrocytes - physiology; Chondrogenesis; Chondrogenesis - physiology; Deacetylation; Down-Regulation - physiology; HDAC1; HEK293 Cells; Histone Deacetylase 1 - genetics; Humans; Promoter Regions, Genetic - genetics; TGF-β1; Transforming Growth Factor beta1 - metabolism; Wnt Signaling Pathway - physiology; Wnt/β-catenin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.10.021

HDAC1 blocks canonical Wnt signaling pathway through down-regulating β-catenin at both transcriptional and post-translational levels. At transcriptional level, HDAC1 binds to ctnnb1 promoter and inhibits β-catenin mRNA synthesis. At the post-translational level, HDAC1 binds to β-catenin protein through its deacetylase domain and promotes degradation of β-catenin. [Display omitted] •Wnt/β-catenin signal has important function in cartilage development.•Wnt/β-catenin signal is down-regulated during TGF-β1-induced chondrogenesis.•HDAC1 suppressed β-catenin expression through direct binding to its promoter.•HDAC1 could also interact with deacetylate β-catenin protein.•HDAC1 may represent a therapeutic target for modulation of cartilage development. Cartilage formation during both embryonic development and bone repairing processes involves mesenchymal stem cells (MSCs) differentiation. Wnt/β-catenin signaling pathway inhibits early chondrogenesis and is down-regulated during Transforming growth factor-β1 (TGF-β1)-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/β-catenin pathway during chondrogenesis. TGF-β1-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 β-catenin was investigated by luciferase assay, chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation (Co-IP) assay and in vitro ubiquitination assay. In this study, we showed that HDAC1 was induced and suppressed β-catenin gene expression through direct binding to its promoter. Besides, HDAC1 could also interact with deacetylate β-catenin protein through its deacetylase domain, which causes degradation of β-catenin. Our results indicate that HDAC1 plays an important role in chondrogenesis and may represent a therapeutic target for modulation of cartilage development.