Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu, Fukuoka 807-8555, Japan.
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu, Fukuoka 807-8555, Japan.
Biochim Biophys Acta Mol Cell Res. 2021 Feb;1868(2):118909. doi: 10.1016/j.bbamcr.2020.118909. Epub 2020 Nov 13.
Mesenchymal stem cells (MSCs) are an attractive cell source for tissue regeneration and repair. However, their low differentiation efficacy currently impedes the development of MSC therapy. Therefore, in this study, we investigated the effects of differentiation-inducing factor-1 (DIF-1) on the differentiation efficacy of bone marrow-derived MSCs (BM-MSCs) into adipogenic or osteogenic lineages. BM-MSCs, which were obtained from Sprague-Dawley rats, were positive for the MSC markers (CD29, CD73, and CD90). DIF-1 alone neither affected cell surface antigen expression nor induced adipogenic or osteogenic differentiation. However, DIF-1 significantly enhanced the effects of adipogenic differentiation stimuli, which were evaluated as the number of oil red-O positive cells and the expression of adipocyte differentiation markers (peroxisome proliferator-activated receptor gamma, adipocyte fatty acid-binding protein, and adiponectin). In contrast, DIF-1 significantly attenuated the effects of osteogenic differentiation stimuli, which were evaluated as alizarin red-S positive calcium deposition, and the expression of osteoblast differentiation markers alkaline phosphatase, runt-related transcription factor 2, and osteopontin. We further investigated the mechanism by which DIF-1 affects MSC differentiation efficacy and found that glycogen synthase kinase-3 was the main factor mediating the action of DIF-1 on the adipogenic differentiation of BM-MSCs, whereas it was only partially involved in osteogenic differentiation. These results suggest that DIF-1 supports MSC differentiation toward the desired cell fate by enhancing the differentiation efficacy.
间充质干细胞（MSCs）是组织再生和修复的有吸引力的细胞来源。然而，它们的低分化效率目前阻碍了 MSC 治疗的发展。因此，在这项研究中，我们研究了分化诱导因子-1（DIF-1）对骨髓来源的间充质干细胞（BM-MSCs）向脂肪生成或成骨谱系分化的效率的影响。从 Sprague-Dawley 大鼠获得的 BM-MSCs 呈 MSC 标志物（CD29、CD73 和 CD90）阳性。DIF-1 单独既不影响细胞表面抗原表达，也不诱导脂肪生成或成骨分化。然而，DIF-1 显著增强了脂肪生成分化刺激的作用，其通过油红-O 阳性细胞的数量和脂肪细胞分化标志物（过氧化物酶体增殖物激活受体γ、脂肪细胞脂肪酸结合蛋白和脂联素）的表达来评估。相比之下，DIF-1 显著减弱了成骨分化刺激的作用，其通过茜素红-S 阳性钙沉积和成骨细胞分化标志物碱性磷酸酶、 runt 相关转录因子 2 和骨桥蛋白的表达来评估。我们进一步研究了 DIF-1 影响 MSC 分化效率的机制，发现糖原合酶激酶-3 是 DIF-1 对 BM-MSCs 脂肪生成分化作用的主要介导因素，而它仅部分参与成骨分化。这些结果表明，DIF-1 通过增强分化效率来支持 MSC 向所需细胞命运分化。
