Unraveling Smad2/4-dependent osteoclast differentiation through transcriptome analysis
Final Report Abstract
The skeletal system is subject to a lifelong remodeling process and is supported by two cell systems, whereby osteoclasts resorb bone and osteoblasts build new bone. Both cell systems are usually in coupled homeostasis, so that normal bone is always formed as part of the remodeling process. Various factors can shift the balance towards increased degradation or remodeling. In this context, we have already shown that various members of the TGF-ßsuperfamily, such as myostatin and activin A, are expressed at high levels in an inflammatory context and play an important role in osteoclast differentiation, therefore responsible for bone loss and joint destruction, e.g. in rheumatoid arthritis. Despite data demonstrating the stimulatory effect of Smad2/3-dependent TGF-β, Activin A and myostatin signaling on osteoclast differentiation, little is known about which target genes are actually responsible for these positive influences. This DFG-funded project therefore aimed to investigate the corresponding expression patterns of osteoclast precursors during differentiation. With the help of transcriptome analyses done by the NGS Competence Center Tübingen and the processing/comparisons by a bioinformatician from the University of Göttingen, important information on the regulation of differentiation-dependent genes and activated signaling pathways during osteoclast differentiation stimulated by members of the TGF-ß superfamily could be obtained within the framework of this DFG project.
