PMID- 28614912
OWN - NLM
STAT- MEDLINE
DCOM- 20180413
LR  - 20240204
IS  - 0219-1032 (Electronic)
IS  - 1016-8478 (Print)
IS  - 1016-8478 (Linking)
VI  - 40
IP  - 6
DP  - 2017 Jun 30
TI  - Peroxisome Proliferator-Activated Receptor alpha Facilitates Osteogenic 
      Differentiation in MC3T3-E1 Cells via the Sirtuin 1-Dependent Signaling Pathway.
PG  - 393-400
LID - 10.14348/molcells.2017.0018 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by 
      lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, 
      thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of 
      osteoblasts may effectively treat diabetic osteoporosis. We previously reported 
      that Sirtuin 1 (Sirt1), a NAD(+)-dependent deacetylase, promotes osteogenic 
      differentiation through downregulation of peroxisome proliferator-activated 
      receptor (PPAR) gamma. We also found that miR-132 regulates osteogenic 
      differentiation by downregulating Sirt1 in a PPARbeta/delta-dependent manner. The 
      ligand-activated transcription factor, PPARalpha, is another isotype of the 
      peroxisome proliferator-activated receptor family that helps maintain bone 
      homeostasis and promot bone formation. Whether the regulatory role of PPARalpha in 
      osteogenic differentiation is mediated via Sirt1 remains unclear. In the present 
      study, we aimed to determine this role and the underlying mechanism by using high 
      glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The 
      results showed that HG-FFA significantly inhibited expression of PPARalpha, Sirt1 and 
      osteogenic differentiation, but these effects were markedly reversed by PPARalpha 
      overexpression. Moreover, siSirt1 attenuated the positive effects of PPARalpha on 
      osteogenic differentiation, suggesting that PPARalpha promotes osteogenic 
      differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed 
      interactions between PPARalpha and Sirt1. These findings indicate that PPARalpha promotes 
      osteogenic differentiation via the Sirt1-dependent signaling pathway.
FAU - Gong, Kai
AU  - Gong K
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
FAU - Qu, Bo
AU  - Qu B
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
FAU - Wang, Cairu
AU  - Wang C
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
FAU - Zhou, Jingsong
AU  - Zhou J
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
FAU - Liao, Dongfa
AU  - Liao D
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
FAU - Zheng, Wei
AU  - Zheng W
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
FAU - Pan, Xianming
AU  - Pan X
AD  - Department of Orthopaedics, Chengdu Military General Hospital, No. 270 Rongdu 
      Road, Chengdu, Sichuan 610083, China.
LA  - eng
PT  - Journal Article
DEP - 20170614
PL  - United States
TA  - Mol Cells
JT  - Molecules and cells
JID - 9610936
RN  - 0 (Culture Media)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (PPAR alpha)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Culture Media/pharmacology
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Fatty Acids, Nonesterified/pharmacology
MH  - Glucose/pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - *Osteogenesis/drug effects
MH  - PPAR alpha/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction
MH  - Sirtuin 1/antagonists & inhibitors/genetics/*metabolism
PMC - PMC5523015
OTO - NOTNLM
OT  - MC3T3-E1
OT  - PPARalpha
OT  - Sirt 1
OT  - diabetic osteoporosis
OT  - osteogenic differentiation
EDAT- 2017/06/16 06:00
MHDA- 2018/04/14 06:00
PMCR- 2017/06/30
CRDT- 2017/06/16 06:00
PHST- 2017/02/06 00:00 [received]
PHST- 2017/04/20 00:00 [revised]
PHST- 2017/05/03 00:00 [accepted]
PHST- 2017/06/16 06:00 [pubmed]
PHST- 2018/04/14 06:00 [medline]
PHST- 2017/06/16 06:00 [entrez]
PHST- 2017/06/30 00:00 [pmc-release]
AID - S1016-8478(23)00627-1 [pii]
AID - molce-40-6-393 [pii]
AID - 10.14348/molcells.2017.0018 [doi]
PST - ppublish
SO  - Mol Cells. 2017 Jun 30;40(6):393-400. doi: 10.14348/molcells.2017.0018. Epub 2017 
      Jun 14.