Osteoarthritis (OA) is the disease characterized by progressive joint destruction without regeneration of new cartilage. Regeneration of cartilage relies on appropriate control of chondrocyte development, whose process is tightly regulated by gene expression. Despite significant progress in identification of important factors regulating gene expression in chondrocyte development, the insight into the mechanism of how these factors function has been limited. One reason is the lack of analysis of how these factors access DNA. Since DNA is stored by “histone”, they usually restrict the access to information in DNA. Modifications that change histones allow contact with DNA and lead to gene expression. A certain set of modifications is thought to form a code, which specifies a pattern of gene expression (known as the Histone Code).

This proposal will seek to decipher the Histone Code in cartilage development and to apply data on cartilage regeneration. With the planned experiments, Dr. Tsuda expects to advance understanding of cartilage cell biology and to generate the basis for new insight into the pathogenesis and treatment of cartilage disorder. Research on the molecular mechanism of chondrogenesis will advance the understanding of skeletal development and has the potential to identify new approaches to the treatment of joint diseases.