Core binding factor β (Cbfβ) is a non‐DNA binding cofactor of Runx2 that potentiates DNA binding. Previously, it has been reported that Cbfβ plays an essential role in osteogenic differentiation and skeletal development by inhibition adipogenesis. Here, we delivered the recombinant Cbfβ protein into human mesenchymal stem cells (MSCs) and triggered osteogenic lineage commitment. The efficient delivery of Cbfβ was achieved by fusing 30Kc19 protein, which is a cell‐penetrating protein derived from the silkworm. After the production of the recombinant Cbfβ‐30Kc19 protein in the Escherichia coli expression system, and confirmation of its intracellular delivery, MSCs were treated with the Cbfβ‐30Kc19 once or twice up to 300 µg/ml. By investigating the upregulation of osteoblast‐specific genes and phenotypical changes, such as calcium mineralization, we demonstrated that Cbfβ‐30Kc19 efficiently induced osteogenic differentiation in MSCs. At the same time, Cbfβ‐30Kc19 suppressed adipocyte formation and downregulated the expression of adipocyte‐specific genes. Our results demonstrate that the intracellularly delivered Cbfβ‐30Kc19 enhances osteogenesis in MSCs, whereas it suppresses adipogenesis by altering the transcriptional regulatory network involved in osteoblast‐adipocyte lineage commitment. Cbfβ‐30Kc19 holds great potential for the treatment of bone‐related diseases, such as osteoporosis, by allowing transcriptional regulation in MSCs, and overcoming the limitations of current therapies.

中文翻译：

---

通过直接递送 Cbfβ 蛋白增强人间充质干细胞的成骨分化。

核心结合因子 β (Cbfβ) 是 Runx2 的非 DNA 结合辅因子，可增强 DNA 结合。以前，据报道，Cbfβ 通过抑制脂肪生成在成骨分化和骨骼发育中起重要作用。在这里，我们将重组 Cbfβ 蛋白递送到人间充质干细胞 (MSC) 中并触发成骨谱系承诺。Cbfβ 的有效传递是通过融合 30Kc19 蛋白实现的，30Kc19 蛋白是一种来源于家蚕的细胞穿透蛋白。在大肠杆菌中产生重组 Cbfβ-30Kc19 蛋白后表达系统，并确认其细胞内递送，用 Cbfβ-30Kc19 处理一次或两次高达 300 µg/ml 的 MSC。通过研究成骨细胞特异性基因的上调和表型变化，如钙矿化，我们证明 Cbfβ-30Kc19 有效诱导 MSCs 的成骨分化。同时，Cbfβ-30Kc19 抑制脂肪细胞形成并下调脂肪细胞特异性基因的表达。我们的结果表明，细胞内递送的 Cbfβ-30Kc19 增强了 MSCs 的成骨作用，而它通过改变参与成骨细胞 - 脂肪细胞谱系定向的转录调控网络来抑制脂肪生成。Cbfβ-30Kc19 通过允许 MSCs 中的转录调节，在治疗骨相关疾病（如骨质疏松症）方面具有巨大潜力，