Altered Expression of Connective Tissue Genes in Postnatal Chondroinduced Human Dermal Fibroblasts

In a novel model for postnatal chondroinduction, normal human dermal fibroblasts (hDFs) cultured with demineralized bone powder (DBP) express chondrocyte features after 7 days. Representational difference analysis (RDA) prior to overt chondroblastogenesis (3 days) revealed altered expression of connective tissue genes (collagens, collagen receptors, and post-translational enzymes). Northern or RT-PCR analysis at 3, 7, 14, or 21 d showed different expression patterns for those genes. COL3A1 was transiently upregulated, whereas upregulation of COL11A1, integrin alpha-11, lysyl oxidase, and lysyl hydroxylase 2 mRNAs persisted for 7 days. Downregulation of decorin was sustained for 21 d. The expression of the post-translational enzymes induced by DBP was unique when compared with human skin and human articular chondrocytes. Thus, the data suggest an "induced chondroblast" stage with a unique connective tissue gene expression profile that may result in a matrix supportive of chondrogenesis by postnatal cells.