PMID- 31793059
OWN - NLM
STAT- MEDLINE
DCOM- 20210728
LR  - 20210728
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 35
IP  - 4
DP  - 2020 Apr
TI  - Direct Reprogramming of Mouse Fibroblasts into Functional Osteoblasts.
PG  - 698-713
LID - 10.1002/jbmr.3929 [doi]
AB  - Although induced pluripotent stem cells hold promise as a potential source of 
      osteoblasts for skeletal regeneration, the induction of pluripotency followed by 
      directed differentiation into osteoblasts is time consuming and low yield. In 
      contrast, direct lineage reprogramming without an intervening stem/progenitor 
      cell stage would be a more efficient approach to generate osteoblasts. We 
      screened combinations of osteogenic transcription factors and identified four 
      factors, Runx2, Osx, Dlx5, and ATF4, that rapidly and efficiently reprogram mouse 
      fibroblasts derived from 2.3 kb type I collagen promoter-driven green fluorescent 
      protein (Col2.3GFP) transgenic mice into induced osteoblast cells (iOBs). iOBs 
      exhibit osteoblast morphology, form mineralized nodules, and express Col2.3GFP 
      and gene markers of osteoblast differentiation. The global transcriptome profiles 
      validated that iOBs resemble primary osteoblasts. Genomewide DNA methylation 
      analysis demonstrates that within differentially methylated loci, the methylation 
      status of iOBs more closely resembles primary osteoblasts than mouse fibroblasts. 
      We further demonstrate that Col2.3GFP(+) iOBs have transcriptome profiles similar 
      to GFP(+) cells harvested from Col2.3GFP mouse bone chips. Functionally, 
      Col2.3GFP(+) iOBs form mineralized bone structures after subcutaneous 
      implantation in immunodeficient mice and contribute to bone healing in a tibia 
      bone fracture model. These findings provide an approach to derive and study 
      osteoblasts for skeletal regeneration. (c) 2019 American Society for Bone and 
      Mineral Research.
CI  - (c) 2019 American Society for Bone and Mineral Research.
FAU - Zhu, Hui
AU  - Zhu H
AUID- ORCID: 0000-0003-0346-3935
AD  - Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Swami, Srilatha
AU  - Swami S
AD  - Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Yang, Pinglin
AU  - Yang P
AD  - Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, 
      USA.
AD  - Veterans Affairs Palo Alto Health Care System, Geriatric Research Education and 
      Clinical Center, Palo Alto, CA, USA.
AD  - Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, China.
FAU - Shapiro, Frederic
AU  - Shapiro F
AD  - Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Wu, Joy Y
AU  - Wu JY
AD  - Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, 
      USA.
LA  - eng
GR  - DP2 OD008466/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191230
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Fibroblasts
MH  - *Induced Pluripotent Stem Cells
MH  - Mice
MH  - Mice, Transgenic
MH  - *Osteoblasts
MH  - Skull
OTO - NOTNLM
OT  - BONE
OT  - FIBROBLAST
OT  - OSTEOBLAST
OT  - REPROGRAMMING
EDAT- 2019/12/04 06:00
MHDA- 2021/07/29 06:00
CRDT- 2019/12/04 06:00
PHST- 2019/06/17 00:00 [received]
PHST- 2019/11/15 00:00 [revised]
PHST- 2019/11/24 00:00 [accepted]
PHST- 2019/12/04 06:00 [pubmed]
PHST- 2021/07/29 06:00 [medline]
PHST- 2019/12/04 06:00 [entrez]
AID - 10.1002/jbmr.3929 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2020 Apr;35(4):698-713. doi: 10.1002/jbmr.3929. Epub 2019 Dec 
      30.