Granéli Cecilia, Karlsson Camilla, Brisby Helena, Lindahl Anders, Thomsen Peter
Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden .
Connect Tissue Res. 2014 Aug;55(4):262-74. doi: 10.3109/03008207.2014.910198. Epub 2014 May 14.
Mesenchymal stem cells (MSCs) can differentiate into several cell types, such as osteoblasts and adipocytes, both in vitro and in vivo. Although these two differentiation pathways are distinct from each other, cross-communication between cells of the two lineages exists both systemically and peripherally in the tissue. The transcription factor PPAR-γ, the main switch in adipogenic differentiation of MSCs, has previously been described to have a negative effect on osteogenic differentiation. The aim of this study was to investigate the effect of PPAR-γ inhibition on osteogenic differentiation of human MSCs, in vitro. Extracellular matrix analysis and quantification of osteogenic markers, revealed how these cells respond when the adipogenic differentiation pathway is blocked during induction of osteogenic differentiation. The inhibition leads to a significant increase in mineralization of the extracellular matrix, as well as an increased activity or up-regulated gene expression of alkaline phosphatase, the key enzyme involved in matrix mineralization. Furthermore, it was also demonstrated by microarray analysis, that PPAR-γ inhibition during osteogenic induction leads to a significant up-regulation of a number of genes related to both osteogenesis and adipogenesis such as c10orf10, leptin, GDF5 and KLF15. In conclusion, inhibition of PPAR-γ during induction of osteogenesis leads to increased osteogenic differentiation of human MSCs.
间充质干细胞（MSCs）在体外和体内均可分化为多种细胞类型，如成骨细胞和脂肪细胞。尽管这两种分化途径相互不同，但这两个谱系的细胞之间在组织中存在全身和局部的交叉通讯。转录因子PPAR-γ是MSCs脂肪生成分化的主要开关，此前已被描述对成骨分化有负面影响。本研究的目的是在体外研究PPAR-γ抑制对人MSCs成骨分化的影响。细胞外基质分析和成骨标志物的定量揭示了在成骨分化诱导过程中脂肪生成分化途径被阻断时这些细胞的反应。这种抑制导致细胞外基质矿化显著增加，以及参与基质矿化的关键酶碱性磷酸酶的活性增加或基因表达上调。此外，微阵列分析还表明，在成骨诱导过程中抑制PPAR-γ会导致一些与成骨和脂肪生成相关的基因显著上调，如c10orf10、瘦素、生长分化因子5（GDF5）和Krüppel样因子15（KLF15）。总之，在成骨诱导过程中抑制PPAR-γ会导致人MSCs的成骨分化增加。
