As robust osteoinductive cytokines, bone morphogenetic proteins (BMPs) play a significant role in bone tissue engineering. Constituted of two different polypeptides, heterodimeric BMPs are more effective than the homodimers in bone formation. While most studies focused on the murine cell lines, such as murine preosteoblasts MC3T3-E1, the role of heterodimeric BMPs in the osteogenic differentiation of human cells remains uncertain, which hinders their application to practical treatment. In this study, we compared the osteoinductive effects of BMP-2/7 heterodimer in human adipose-derived stem cells (hASCs) with their homodimers BMP-2 and BMP-7, in which MC3T3-E1 cells were utilized as a positive control. The results indicated that BMP-2/7 was not a stronger inducer during the osteogenic differentiation of hASCs as that for MC3T3-E1, and extracellular-signal-regulated kinase signaling played a role in the different effects of BMP-2/7 between hASCs and MC3T3-E1. Our study demonstrates the osteoinductive effects of heterodimeric BMP-2/7 present in a cell-specific pattern and cautions should be taken when applying heterodimeric BMP-2/7 to clinical practice.

作为强大的骨诱导细胞因子，骨形态发生蛋白（BMP）在骨组织工程中起重要作用。由两种不同的多肽组成，异二聚体BMP在骨形成方面比同二聚体更有效。尽管大多数研究都集中在鼠类成骨细胞MC3T3-E1等鼠类细胞系上，但异二聚体BMP在人类细胞成骨分化中的作用仍然不确定，这阻碍了它们在实际治疗中的应用。在这项研究中，我们比较了BMP-2 / 7异二聚体在人脂肪干细胞（hASCs）与同二聚体BMP-2和BMP-7中的骨诱导作用，其中MC3T3-E1细胞被用作阳性对照。结果表明，在hASC的成骨分化过程中，BMP-2 / 7并非MC3T3-E1的强诱导剂，细胞外信号调节激酶信号转导在hASC和MC3T3-E1之间的BMP-2 / 7的不同作用中起作用。我们的研究证明了异二聚体BMP-2 / 7以细胞特异性模式存在的骨诱导作用，在将异二聚体BMP-2 / 7应用于临床实践时应谨慎行事。