Neubauer Markus, Fischbach Claudia, Bauer-Kreisel Petra, Lieb Esther, Hacker Michael, Tessmar Joerg, Schulz Michaela B, Goepferich Achim, Blunk Torsten
Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, D-93040 Regensburg, Germany.
FEBS Lett. 2004 Nov 5;577(1-2):277-83. doi: 10.1016/j.febslet.2004.10.020.
Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of lineages, including bone, cartilage, or fat, depending on the inducing stimuli and specific growth and differentiation factors. It is widely acknowledged that basic fibroblast growth factor (bFGF) modulates chondrogenic and osteogenic differentiation of MSCs, but thorough investigations of its effects on adipogenic differentiation are lacking. In this study, we demonstrate on the cellular and molecular level that supplementation of bFGF in different phases of cell culture leads to a strong enhancement of adipogenesis of MSCs, as induced by an adipogenic hormonal cocktail. In cultures receiving bFGF, mRNA expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2), a key transcription factor in adipogenesis, was upregulated even prior to adipogenic induction. In order to investigate the effects of bFGF on PPARgamma ligand-induced adipogenic differentiation, the thiazolidinedione troglitazone was administered as a single adipogenic inducer. Basic FGF was demonstrated to also strongly increase adipogenesis induced by troglitazone, that is, bFGF clearly increased the responsiveness of MSCs to a PPARgamma ligand.
间充质干细胞（MSCs）能够根据诱导刺激以及特定的生长和分化因子分化为多种谱系，包括骨、软骨或脂肪。人们普遍认为，碱性成纤维细胞生长因子（bFGF）可调节MSCs的软骨生成和成骨分化，但对其在脂肪生成分化方面作用的深入研究尚缺。在本研究中，我们在细胞和分子水平上证明，在细胞培养的不同阶段补充bFGF会导致由脂肪生成激素混合物诱导的MSCs脂肪生成显著增强。在接受bFGF的培养物中，脂肪生成关键转录因子过氧化物酶体增殖物激活受体γ2（PPARγ2）的mRNA表达甚至在脂肪生成诱导之前就上调了。为了研究bFGF对PPARγ配体诱导的脂肪生成分化的影响，使用噻唑烷二酮曲格列酮作为单一脂肪生成诱导剂。结果表明，碱性成纤维细胞生长因子也能显著增加曲格列酮诱导的脂肪生成，即bFGF明显增强了MSCs对PPARγ配体的反应性。
