title: Histone deacetylase1 promotes TGF-β1-mediated early chondrogenesis through down-regulating canonical Wnt signaling.
abstract: 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.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China. Electronic address: xjhuang@sibs.ac.cn.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China. Electronic address: xujiajia@sibs.ac.cn.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China. Electronic address: mingjian77@gmail.com.
authors.forename: Mingjian
authors.initials: M
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China. Electronic address: owllj@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China. Electronic address: lmdai@sibs.ac.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Dai
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China; Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200011, China. Electronic address: krdai@163.com.
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200031, China; Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200011, China. Electronic address: xlzhang@sibs.ac.cn.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
mesh_terms: D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D056284:Histone Deacetylase 1
keywords: Chondrogenesis; Deacetylation; HDAC1; TGF-β1; Wnt/β-catenin