Mizoshiri N, Kishida T, Yamamoto K, Shirai T, Terauchi R, Tsuchida S, Mori Y, Ejima A, Sato Y, Arai Y, Fujiwara H, Yamamoto T, Kanamura N, Mazda O, Kubo T
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Biochem Biophys Res Commun. 2015 Nov 27;467(4):1110-6. doi: 10.1016/j.bbrc.2015.10.098. Epub 2015 Oct 22.
Osteoblasts play essential roles in bone formation and regeneration, while they have low proliferation potential. Recently we established a procedure to directly convert human fibroblasts into osteoblasts (dOBs). Transduction of Runx2 (R), Osterix (X), Oct3/4 (O) and L-myc (L) genes followed by culturing under osteogenic conditions induced normal human fibroblasts to express osteoblast-specific genes and produce calcified bone matrix both in vitro and in vivo Intriguingly, a combination of only two factors, Oct3/4 and L-myc, significantly induced osteoblast-like phenotype in fibroblasts, but the mechanisms underlying the direct conversion remains to be unveiled.
We examined which Oct family genes and Myc family genes are capable of inducing osteoblast-like phenotypic conversion.
As result Oct3/4, Oct6 and Oct9, among other Oct family members, had the capability, while N-myc was the most effective Myc family gene. The Oct9 plus N-myc was the best combination to induce direct conversion of human fibroblasts into osteoblast-like cells.
The present findings may greatly contribute to the elucidation of the roles of the Oct and Myc proteins in osteoblast direct reprogramming. The results may also lead to establishment of novel regenerative therapy for various bone resorption diseases.
成骨细胞在骨形成和再生中发挥着重要作用，但其增殖潜能较低。最近我们建立了一种将人成纤维细胞直接转化为成骨细胞（dOBs）的方法。转导Runx2（R）、Osterix（X）、Oct3/4（O）和L-myc（L）基因，然后在成骨条件下培养，可诱导正常人成纤维细胞在体外和体内表达成骨细胞特异性基因并产生钙化骨基质。有趣的是，仅Oct3/4和L-myc这两种因子的组合就能显著诱导成纤维细胞出现成骨细胞样表型，但直接转化的潜在机制仍有待揭示。
我们研究了哪些Oct家族基因和Myc家族基因能够诱导成骨细胞样表型转化。
结果显示，Oct家族成员中的Oct3/4、Oct6和Oct9具有这种能力，而N-myc是最有效的Myc家族基因。Oct9与N-myc的组合是诱导人成纤维细胞直接转化为成骨细胞样细胞的最佳组合。
本研究结果可能对阐明Oct和Myc蛋白在成骨细胞直接重编程中的作用有很大贡献。这些结果也可能有助于建立针对各种骨吸收疾病的新型再生疗法。
