Zhou Xiaopeng, Tao Yiqing, Wang Jin, Liang Chengzhen, Wang Jun, Li Hao, Chen Qixin
Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, Zhejiang , People's Republic of China.
Growth Factors. 2015 Feb;33(1):23-30. doi: 10.3109/08977194.2014.969420. Epub 2014 Oct 1.
Human mesenchymal stem cells (MSCs) are reported to have the capability of differentiating towards nucleus pulposus (NP)-like phenotype under specific culture conditions. So far, the effects of fibroblast growth factor (FGF)-2 and the cocktail effects of transforming growth factor (TGF)-beta and FGF-2 on MSCs remain unclear. Therefore, we designed this study to clarify these effects. MSCs were cultured in conditioned medium containing FGF-2 or TGF-beta/FGF-2, and compared with basal or TGF-beta medium. The groups with FGF-2 showed the increase of cell proliferation. Functional gene markers and novel NP markers decreased in FGF-2 group, together with functional protein expression. Pho-ERK1/2 and pho-Smad3 differed significantly in the two conditioned groups. All these results suggest FGF-2 promotes MSCs' proliferation, synergistically with TGF-beta. However, FGF-2 plays a negative role in cartilage homeostasis. We also demonstrate that FGF-2 has no positive effect in differentiating MSCs into NP-like cells, but hinders the acceleration effect of TGF-beta.
据报道,人骨髓间充质干细胞(MSCs)在特定培养条件下具有向髓核(NP)样表型分化的能力。到目前为止,成纤维细胞生长因子(FGF)-2以及转化生长因子(TGF)-β和FGF-2的联合作用对间充质干细胞的影响仍不清楚。因此,我们设计了本研究以阐明这些影响。将间充质干细胞培养于含有FGF-2或TGF-β/FGF-2的条件培养基中,并与基础培养基或TGF-β培养基进行比较。含FGF-2的组细胞增殖增加。FGF-2组中功能基因标志物和新型NP标志物减少,同时功能蛋白表达也减少。两个条件培养基组中磷酸化细胞外信号调节激酶1/2(Pho-ERK1/2)和磷酸化Smad3有显著差异。所有这些结果表明,FGF-2协同TGF-β促进间充质干细胞的增殖。然而,FGF-2在软骨稳态中起负面作用。我们还证明,FGF-2在将间充质干细胞分化为NP样细胞方面没有积极作用,反而阻碍了TGF-β的促进作用。