PMID- 25524638
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20191008
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 33
IP  - 4
DP  - 2015 Apr
TI  - p53 loss increases the osteogenic differentiation of bone marrow stromal cells.
PG  - 1304-19
LID - 10.1002/stem.1925 [doi]
AB  - The tumor suppressor, p53, plays a critical role in suppressing osteosarcoma. 
      Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal 
      stem cells) have been suggested to give rise to osteosarcomas. However, the role 
      of p53 in BMSCs has not been extensively explored. Here, we report that p53 
      regulates the lineage choice of mouse BMSCs (mBMSCs). Compared to mBMSCs with 
      wild-type p53, mBMSCs deficient in p53 have enhanced osteogenic differentiation, 
      but with similar adipogenic and chondrogenic differentiation. The role of p53 in 
      inhibiting osteogenic lineage differentiation is mainly through the action of 
      Runx2, a master transcription factor required for the osteogenic differentiation 
      of mBMSCs. We find that p53 indirectly represses the expression of Runx2 by 
      activating the microRNA-34 family, which suppresses the translation of Runx2. 
      Since osteosarcoma may derive from BMSCs, we examined whether p53 has a role in 
      the osteogenic differentiation of osteosarcoma cells and found that osteosarcoma 
      cells with p53 deletion have higher levels of Runx2 and faster osteogenic 
      differentiation than those with wild-type p53. A systems biology approach reveals 
      that p53-deficient mBMSCs are more closely related to human osteosarcoma while 
      mBMSCs with wild-type p53 are similar to normal human BMSCs. In summary, our 
      results indicate that p53 activity can influence cell fate specification of 
      mBMSCs, and provide molecular and cellular insights into the observation that p53 
      loss is associated with increased osteosarcoma incidence.
CI  - (c) 2014 AlphaMed Press.
FAU - He, Yunlong
AU  - He Y
AD  - Cancer and Stem Cell Epigenetics Section, Laboratory of Cancer Biology and 
      Genetics.
FAU - de Castro, Luis F
AU  - de Castro LF
FAU - Shin, Min Hwa
AU  - Shin MH
FAU - Dubois, Wendy
AU  - Dubois W
FAU - Yang, Howard H
AU  - Yang HH
FAU - Jiang, Shunlin
AU  - Jiang S
FAU - Mishra, Pravin J
AU  - Mishra PJ
FAU - Ren, Ling
AU  - Ren L
FAU - Gou, Hongfeng
AU  - Gou H
FAU - Lal, Ashish
AU  - Lal A
FAU - Khanna, Chand
AU  - Khanna C
FAU - Merlino, Glenn
AU  - Merlino G
FAU - Lee, Maxwell
AU  - Lee M
FAU - Robey, Pamela G
AU  - Robey PG
FAU - Huang, Jing
AU  - Huang J
LA  - eng
GR  - Z99 CA999999/Intramural NIH HHS/United States
GR  - ZIA BC011158-06/Intramural NIH HHS/United States
GR  - ZIA BC011504-01/Intramural NIH HHS/United States
GR  - ZIA BC011504-02/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*physiology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Humans
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Osteogenesis/*physiology
MH  - Tumor Suppressor Protein p53/*deficiency
PMC - PMC4376591
MID - NIHMS649671
OTO - NOTNLM
OT  - Bone marrow stromal cells
OT  - Mesenchymal stem cells
OT  - Osteosarcoma
OT  - p53
COIS- Conflict of Interests The authors declare no conflict of interest.
EDAT- 2014/12/20 06:00
MHDA- 2016/01/16 06:00
PMCR- 2016/04/01
CRDT- 2014/12/20 06:00
PHST- 2014/05/15 00:00 [received]
PHST- 2014/10/22 00:00 [revised]
PHST- 2014/11/07 00:00 [accepted]
PHST- 2014/12/20 06:00 [entrez]
PHST- 2014/12/20 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - 10.1002/stem.1925 [doi]
PST - ppublish
SO  - Stem Cells. 2015 Apr;33(4):1304-19. doi: 10.1002/stem.1925.