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.