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Calcif Tissue Int (2006) 79:169[C0]178DOI: 10.1007/s00223-006-0083-6Laboratory Investigations Runx2 Overexpression Enhances Osteoblastic Dierentiation and Mineralization in Adipose - Derived Stem Cells in vitro and in vivoX. Zhang,1 M. Yang,3 L. Lin,1 P. Chen,2 K. T. Ma,2 C. Y. Zhou,2 Y. F. Ao11Department of Sports Medicine, Peking University Third Hospital, Beijing 100083, China2Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China3Department of Orthopedics, Wannan Medical College Yijishan Hospital, Wuhu 241001, China Received: 22 March 2006 / Accepted: 22 May 2006 / Online publication: 11 September 2006Abstract. Like bone marrow stromal cells, adipose tissue-derived stem cells (ADSCs) possess multilineage potential, a capacity for self-renewal and long-term viability. To conrm whether ADSCs represent a promising source of cells for gene-enhanced bone tissue-engineering, the osteogenic potential of ADSCs under the control of certain osteoinductive genes has been evaluated. Runx2, a transcription factor at the downstream end of bone morphogenetic protein (BMP) signaling pathways, is essential for osteoblast dierentiation and bone formation. In this study we used adenovirus vector to deliver Runx2 to ADSCs and then examined the enhancement of osteogenic activity. Overexpression of Runx2 inhibited adipogenesis, as demonstrated by suppression of LPL and PPARc expression at the mRNA level and reduced lipid droplet formation. Moreover, ADSCs transduced with AdRunx2 underwent rapid and marked osteoblast dierentiation as determined by osteoblastic gene expression, alkaline phosphatase activity and mineral deposition. Additionally, histological examination revealed that implantation of Runx2 modied ADSCs could induce mineral deposition and bone-like tissue formation in vivo. These results conrmed, rstly, the ability of Runx2 to promote osteogenesis and cell dierentiation and, secondly, the competence of ADSCs as target cells for bone tissue engineering. Our work demonstrates a potential new approach for bone repair using Runx2-modied ADSCs for bone tissue engineering.Key words: Adipose[C0]derived stem cells Runx2 Gene therapy Dierentiation OsteogenesisCurrently, there are no completely eective treatments for massive segmental bone defects and non-healing fractures. Conventional autograft or allograft trans- plantation is severely limited by the availability of donor tissue sources [1]. Therapy with recombinant bone morphogenetic proteins (rBMPs) appears promising [2[C0]4]. However, without optimal matrices for controlled and sustained BMP delivery, the short biological half-life and immunogenicity of rBMPs limit the use of this approach [1]. With advances in cell...