Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose -: derived stem cells in vitro and in vivo
Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose -: derived stem cells in vitro and in vivo
复制标题
Runx2 过表达增强脂肪干细胞的体外和体内成骨细胞分化和矿化
DOI：
10.1007/s00223-006-0083-6
复制
发表时间：
2006-09-01
影响因子：
4.2
通讯作者：
Ao, Y. F.
中科院分区：
文献类型：
--
作者：
Zhang, X.;Yang, M.;Ao, Y. F.
与骨髓基质细胞一样，脂肪组织来源的干细胞（ADSC）具有多谱系潜能，自我更新和长期存活的能力。为了确认ADSC是否是基因增强骨组织工程的有希望的细胞来源，我们评估了ADSC在某些骨诱导基因控制下的成骨潜力。Runx 2是骨形态发生蛋白（BMP）信号传导通路下游的转录因子，对成骨细胞分化和骨形成至关重要。在本研究中，我们使用腺病毒载体将Runx 2递送到ADSCs，然后检测成骨活性的增强。Runx 2的过表达抑制脂肪形成，如通过在mRNA水平抑制LPL和PPARgamma表达和减少脂滴形成所证明的。此外，ADSCs与Ad-Runx 2转导进行快速和显着的成骨细胞分化，成骨细胞基因表达，碱性磷酸酶活性和矿物质沉积确定。此外，组织学检查显示，Runx 2修饰的ADSCs植入体内可诱导矿物质沉积和骨样组织形成。这些结果证实，首先，Runx 2促进成骨和细胞分化的能力，其次，ADSCs作为骨组织工程靶细胞的能力。我们的工作证明了使用Runx 2修饰的ADSCs进行骨组织工程的骨修复的潜在新方法。
Like bone marrow stromal cells, adipose tissue-derived stem cells (ADSCs) possess multilineage potential, a capacity for self-renewal and long-term viability. To confirm 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 differentiation 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 PPARgamma expression at the mRNA level and reduced lipid droplet formation. Moreover, ADSCs transduced with Ad-Runx2 underwent rapid and marked osteoblast differentiation as determined by osteoblastic gene expression, alkaline phosphatase activity and mineral deposition. Additionally, histological examination revealed that implantation of Runx2 modified ADSCs could induce mineral deposition and bone-like tissue formation in vivo. These results confirmed, firstly, the ability of Runx2 to promote osteogenesis and cell differentiation 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-modified ADSCs for bone tissue engineering.