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

多能细胞的细胞命运决定、干细胞的增殖、分化、成熟和维持是骨骼纵向生长过程中的基本细胞事件。主要转录因子Sox9是形成永久软骨和替代软骨所必需的。在胚胎发育过程中，Sox9在所有的骨软骨祖细胞和软骨细胞中表达，在其他功能中，它是间质凝聚和抑制增殖的软骨细胞的早熟肥大转化所必需的。我们通过RNAi干扰(RNAi)在体外抑制了成人骨髓间充质干细胞(MSC)中的Sox9。我们的研究目的是确定Sox9在成人MSC中的作用及其对成骨软骨分化能力和细胞存活的影响。(1)阐明Sox9在控制MSC增殖和活力中的作用。(2)研究Sox9影响细胞存活的信号转导途径。(3)从肥大转化和成骨的角度研究Sox9抑制的MSC向成骨细胞分化的能力。目前还没有关于Sox9在MSC中表达和功能调节的药理学方法的报道。因此，解开Sox9调控在多能间充质干细胞中的后果可能有助于开发治疗软骨病变和退行性关节和椎间盘疾病的概念。

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.