Transduction of Oct6 or Oct9 gene concomitant with Myc family gene induced osteoblast-like phenotypic conversion in normal human fibroblasts.
BACKGROUND
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.


METHODS
We examined which Oct family genes and Myc family genes are capable of inducing osteoblast-like phenotypic conversion.


RESULTS
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.


CONCLUSIONS
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.
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
N
N
Mizoshiri
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
T
T
Kishida
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
K
K
Yamamoto
Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
T
T
Shirai
Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
R
R
Terauchi
Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
S
S
Tsuchida
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Y
Y
Mori
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
A
A
Ejima
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Y
Y
Sato
Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Y
Y
Arai
Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
H
H
Fujiwara
Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
T
T
Yamamoto
Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
N
N
Kanamura
Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: mazda@koto.kpu-m.ac.jp.
O
O
Mazda
Department of Orthopaedics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
T
T
Kubo
D005347:Fibroblasts / Q000378:metabolism*; D016259:Genes, myc; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010006:Osteoblasts / Q000378:metabolism*; D010641:Phenotype; D014161:Transduction, Genetic
D027701:Organic Cation Transport Proteins; C467737:SLC22A16 protein, human
Direct reprogramming; N-Myc; Oct9; Osteoblast