Steven Abramson, MD

Our lab is interested in the cytokine, growth factors, extracellular matrix proteins and integrins involved in the chondrocyte signaling pathways and molecular mechanisms that regulate the biology of chondrocytes and bone cells. Basic research is also carried out on the cellular and molecular mechanisms underlying chondrocyte differentiation and maturation. Currently we are employing global gene expression technique such as microarray to study changes in gene expression in osteoarthritis cartilage as compared to non-arthritic cartilage. We are also currently involved in characterizing the promoters of dysregulated genes in OA with promoter analyses software to characterize and study the influence of transcription factors on these genes. Furthermore, recent evidence suggests that during OA chondrocytes undergo a phenotypic modulation to hypertrophic state which are considered as degradative chondrocytes. Hypertrophic chondrocytes synthesize cartilage-degrading proteases and thus probably play a critical role in the progression of the disease. The phenotype of normal chondrocytes is stabilized by the epigenetic status of the cell such as hyper or hypo methylation of target gene promoters. This raises the question as to whether the destabilization of the chondrocytic phenotype in OA is at least, in part, the result of changes in this epigenetic status. Recently, we have undertaken to study epigenetic changes including micro RNA expression, which allows us to study the transcriptional and translational regulation of genes.

Furthermore, our laboratory has long standing interest in the functions for nitric oxide (NO) and prostaglandin E2 in the activation of MAP kinase signaling, protease synthesis and cellular death in chondrocyte and synovial fibroblast. Recently, we identified a novel latent tumor growth factor-beta1 (TGF-beta1) activating an extracellular matrix protein F-spondin. F-spondin has not been studied in differentiation of chondrocyte, endochondral ossification, cartilage matrix metabolism and pathological mineralization process. We are planning to develop an F-spondin knock out mouse to explore the functions of F-spondin and TGFb-1 in the development of OA. The fundamental knowledge obtained from these studies is crucial for understanding the pathogenesis and treatment of diseases such as osteoarthritis and rheumatoid arthritis.