PMID- 31245876
OWN - NLM
STAT- MEDLINE
DCOM- 20200908
LR  - 20200908
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 11
DP  - 2019 Nov
TI  - Identification of Gli1-interacting proteins during simvastatin-stimulated 
      osteogenic differentiation of bone marrow mesenchymal stem cells.
PG  - 18979-18994
LID - 10.1002/jcb.29221 [doi]
AB  - Simvastatin has been shown to promote osteogenic differentiation of bone marrow 
      mesenchymal stem cells (BMSCs). Our study aimed to illuminate the underlying 
      mechanism, with a specific focus on the role of Hedgehog signaling in this 
      process. BMSCs cultured with or without 10(-7)  mol/L simvastatin were subjected 
      to evaluation of osteogenic differentiation capacity. Osteogenic markers such as 
      type 1 collagen (COL1) and osteocalcin (OCN), as well as key molecules of 
      Hedgehog signaling molecules, were examined by Western blot and real-time 
      polymerase chain reaction (PCR). Co-immunoprecipitation and mass spectrometry 
      assays were applied to screen for Gli1-interacting proteins. Cyclopamine (Cpn) 
      was used as a Hedgehog signaling inhibitor. Our results indicated that 
      simvastatin increased alkaline phosphatase (ALP) activity; mineralization of 
      extracellular matrix; mRNA expression of ALP, COL1, and OCN; and expression and 
      nuclear translocation of Gli1. Contrasting effects were observed in Cpn-exposed 
      groups, but were partially rescued by the simvastatin treatment. Gene Ontology 
      and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that 
      Gli1-interacting proteins were primarily associated with mitogen-activated 
      protein kinase (MAPK) (P = 7.04E(-04) ), hippo, insulin, and glucagon signaling. 
      Further, hub genes identified by protein-protein interaction network analysis 
      included Gli1-interacting proteins such as Ppp2r1a, Rac1, Etf1, and XPO1/CRM1. In 
      summary, the current study showed that the mechanism by which simvastatin 
      stimulates osteogenic differentiation of BMSCs involves activation of Hedgehog 
      signaling, as indicated by interactions with Gli1 and, most notably, the MAPK 
      signaling pathway.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Chi, Bojing
AU  - Chi B
AUID- ORCID: 0000-0001-7083-3380
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
AD  - Department of Geriatrics, Affiliated Hospital of North China University of 
      Science and Technology, Tangshan, China.
FAU - Fan, Xinhao
AU  - Fan X
AD  - Department of Stomatology, Kailuan General Hospital, Tangshan, China.
FAU - Li, Zhengxiao
AU  - Li Z
AD  - Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, China.
FAU - Liu, Guangyuan
AU  - Liu G
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
FAU - Zhang, Guobin
AU  - Zhang G
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
FAU - Xu, Hong
AU  - Xu H
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
FAU - Li, Zhiguo
AU  - Li Z
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
FAU - Lian, Qiangqiang
AU  - Lian Q
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
FAU - Xing, Lei
AU  - Xing L
AD  - Department of Geriatrics, Affiliated Hospital of North China University of 
      Science and Technology, Tangshan, China.
FAU - Tian, Faming
AU  - Tian F
AD  - Medical Research Center, North China University of Science and Technology, 
      Tangshan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190627
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Gli1 protein, rat)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*metabolism
MH  - Cell Differentiation/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - MAP Kinase Signaling System/drug effects
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Osteogenesis/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Simvastatin/*pharmacology
MH  - Zinc Finger Protein GLI1/*metabolism
OTO - NOTNLM
OT  - Gli1
OT  - Hedgehog signaling pathway
OT  - osteogenic differentiation
OT  - simvastatin
EDAT- 2019/06/28 06:00
MHDA- 2020/09/09 06:00
CRDT- 2019/06/28 06:00
PHST- 2018/11/06 00:00 [received]
PHST- 2019/05/31 00:00 [revised]
PHST- 2019/05/31 00:00 [accepted]
PHST- 2019/06/28 06:00 [pubmed]
PHST- 2020/09/09 06:00 [medline]
PHST- 2019/06/28 06:00 [entrez]
AID - 10.1002/jcb.29221 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Nov;120(11):18979-18994. doi: 10.1002/jcb.29221. Epub 2019 
      Jun 27.