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）是用于组织再生和修复的有吸引力的细胞来源。然而，它们的低分化功效目前阻碍了MSC疗法的发展。因此，在这项研究中，我们调查了分化诱导因子1（DIF-1）对骨髓来源的MSC（BM-MSC）分化为成脂或成骨谱系的功效。从Sprague-Dawley大鼠获得的BM-MSC对MSC标记（CD29，CD73和CD90）呈阳性。单独的DIF-1既不影响细胞表面抗原表达也不诱导脂肪形成或成骨分化。但是，DIF-1显着增强了成脂分化刺激的作用，它们被评估为油红-O阳性细胞的数目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。相比之下，DIF-1显着减弱了成骨分化刺激的作用，该作用被评估为茜素红-S阳性钙沉积，以及成骨细胞分化标记碱性磷酸酶，欠缺相关转录因子2和骨桥蛋白的表达。我们进一步研究了DIF-1影响MSC分化功效的机制，发现糖原合酶激酶3是介导DIF-1对BM-MSCs成脂分化作用的主要因素，而它仅部分参与成骨差异化。