[Direct cell reprogramming to chondrogenic cells from dermal fibroblast culture]

In regenerative medicine, converting one cell type to another type associates with altering epigenome of cells without changing their genome sequences. Since development of iPS cells, it has become possible to convert cell types through altering epigenome by transducing plural kye transcription factors into cells. We found that transduction of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) into mouse dermal fibroblasts results in direct induction of chondrogeni cells. Directly induced chondrogenic cells showed highly methylated promoter sequences of fibroblastic markers, type I collagen genes. These induced cells, when transplanted into nude mice, produced hyaline cartilage without expressing type I collagen, suggesting that type I collagen genes were silenced in these induced chondrogenic cells in vivo . It is also expected to apply cell reprogramming technique to treatment of osteoarthritis in some aspects including reversion of degenerated fibrocartilage into hyalinecartilage.