Early shifts in gene expression during chondroinduction of human dermal fibroblasts

Treatment options for damaged articular cartilage are limited because of th at. tissue's poor capacity for repair. Possible approaches to this problem are to stimulate, cartilage matrix production in situ or to engineer replac ement tissue. Both of these approaches would benefit from a detailed unders tanding of the molecular mechanisms of chondroblast differentiation, In pre vious studies, we described a novel in vitro model of postnatal chondroblas t differentiation. That model of induced chondrogenesis was used to test th e hypothesis that cellular interactions with demineralized bone powder (DBP ) would induce specific, early shifts in gene expression, prior to the expr ession of cartilage matrix genes. Differentially expressed genes were ident ified by representational difference analysis of human dermal fibroblasts c ultured for 3 days with DBP in three-dimensional collagen sponges. Genes th at were upregulated by DBP comprised several functional classes, including cytoskeletal elements, protein synthesis and trafficking, and transcription al regulation. kinetic analysis of gene expression over 21 days showed that vigilin was transiently upregulated on day 3. In contrast, expression of c artilage signature genes continued to increase. These results are an import ant step toward complete characterization of the mechanisms by which DBP in duces chondroblastic differentiation in postnatal cells. (C) 2001 Academic Press.