Sox9 and adult bone marrow derived mesenchymal stem cells (MSC)

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Cell-fate determination of pluripotent cells, cell proliferation, differentiation, maturation and maintenance of stem cells are essential cellular events during longitudinal skeletal growth. Master transcription factor Sox9 is required for formation of both permanent and replacement cartilage. During embryogenesis Sox9 is expressed in all osteochondroprogenitor cells and chondrocytes, where, among other functions, it is required for mesenchymal condensation and inhibition of precocious hypertrophic conversion of proliferating chondrocytes. We have inhibited Sox9 in vitro in adult bone marrow derived mesenchymal stem cells (MSC) by RNAi interference (RNAi). The aim of our study is to determine the role of Sox9 in adult MSC and its impact on osteochondrogenic differentiation capacity and cell survival. (1) We want to delineate the role of Sox9 in controlling proliferation and vitality of MSC. (2) We want to delineate the underlying signal transduction pathway mediating Sox9 effects on cell survival. (3) We want to determine osteo-chondrogenic differentiation capacity of Sox9 inhibited MSC with particular respect to hypertrophic conversion and osteogenesis. No pharmacological approach to the regulation of Sox9 expression and function in MSC has been reported as to now. Thus, unraveling the consequences of Sox9 regulation in multipotent MSC might help to develop concepts for treatment of chondral lesions and degenerative joint and disc diseases.