Evidence map›Paper›PMID 25918395›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Direct conversion of human fibroblasts into functional osteoblasts by defined factors.

Kenta Yamamoto, Tsunao Kishida, Yoshiki Sato, Keisuke Nishioka, Akika Ejima, Hiroyoshi Fujiwara, Toshikazu Kubo, Toshiro Yamamoto, Narisato Kanamura, Osam Mazda

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 131 citations in OpenAlex.

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  8. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
    Review
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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 3 countries.

Kenta YamamotoDepartments of Immunology, Dental Medicine, and.
Tsunao KishidaDepartments of Immunology.
Yoshiki SatoDepartments of Immunology, Dental Medicine, and.
Keisuke NishiokaDepartments of Immunology.
Akika EjimaDepartments of Immunology.
Hiroyoshi FujiwaraOrthopedics, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Toshikazu KuboOrthopedics, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Toshiro YamamotoDental Medicine, and.
Narisato KanamuraDental Medicine, and.
Osam MazdaDepartments of Immunology, mazda@koto.kpu-m.ac.jp.
University of Dental Medicine · MMKyoto Prefectural University of Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoblasts produce calcified bone matrix and contribute to bone formation and remodeling. In this study, we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some defined factors and culturing in osteogenic medium. Osteoblast-specific transcription factors, Runt-related transcription factor 2 (Runx2), and Osterix, in combination with Octamer-binding transcription factor 3/4 (Oct4) and L-Myc (RXOL) transduction, converted ∼ 80% of the fibroblasts into osteocalcin-producing cells. The directly converted osteoblasts (dOBs) induced by RXOL displayed a similar gene expression profile as normal human osteoblasts and contributed to bone repair after transplantation into immunodeficient mice at artificial bone defect lesions. The dOBs expressed endogenous Runx2 and Osterix, and did not require continuous expression of the exogenous genes to maintain their phenotype. Another combination, Oct4 plus L-Myc (OL), also induced fibroblasts to produce bone matrix, but the OL-transduced cells did not express Osterix and exhibited a more distant gene expression profile to osteoblasts compared with RXOL-transduced cells. These findings strongly suggest successful direct reprogramming of fibroblasts into functional osteoblasts by RXOL, a technology that may provide bone regeneration therapy against bone disorders.

Indexed as

Gene Expression RegulationAnimalsBone and BonesBone RegenerationBone RemodelingCalcinosisCore Binding Factor Alpha 1 SubunitFibroblastsGene Expression ProfilingGingivaHumansMaleMiceMice, Inbred NODMice, SCIDOctamer Transcription Factor-3Core Binding Factor Alpha 1 SubunitOctamer Transcription Factor-3POU5F1 protein, humanProto-Oncogene Proteins c-mycRNA, MessengerRUNX2 protein, humanSP7 protein, humanSp7 Transcription FactorTranscription Factorsdirect reprogrammingosteoblastsregenerative medicine

Identifiers

PMID25918395
PMCPMC4434770
OpenAlexW2063626006

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.