PMID- 33516884
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20210831
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 544
DP  - 2021 Mar 12
TI  - Exendin-4 promotes bone formation in diabetic states via HDAC1-Wnt/beta-catenin 
      axis.
PG  - 8-14
LID - S0006-291X(21)00074-7 [pii]
LID - 10.1016/j.bbrc.2021.01.039 [doi]
AB  - Exendin-4 has been found to have hypoglycemic effect and prevent bone loss in 
      diabetic patients, but its mechanism of preventing bone loss is still unclear. In 
      this study, high-fat diet combined with streptozotocin was used to establish type 
      2 diabetes mellitus (T2DM) mice, and bone marrow mesenchyme stem cells (BMSCs) 
      were isolated for osteogenic induction in vitro. Alizarin red staining and ALP 
      activity detection were used to observe the effect of exendin-4 on osteogenic 
      differentiation of BMSCs. Western blot was used to detect the proteins expression 
      in BMSCs. In vivo, the effects of exendin-4 treatment on body weight, blood 
      glucose, bone density and bone quality of T2DM mice were observed by treatment 
      with exendin-4. The results showed that exendin-4 promoted osteogenic 
      differentiation of T2DM derived BMSCs, down-regulated histone deacetylase 1 
      (HDAC1) and p-beta-Catenin proteins expression, and up-regulated Wnt3, beta-Catenin and 
      runt-related transcription factor 2 (Runx 2) proteins expression. In vivo, 
      exendin-4 effectively suppressed the blood glucose and increased body weight of 
      T2DM mice, and significantly improved bone density and bone quality of the right 
      tibia. Interestingly, by over-expression of HDAC1 in BMSCs, the effect of 
      exendin-4 on promoting osteogenic differentiation of BMSCs was attenuated, and 
      the regulation of Wnt3a, beta-Catenin, p-beta-Catenin or Runx2 proteins were reversed. 
      By injecting adenovirus containing HDAC1 into the right tibia of mice, the effect 
      of exendin-4 on bone density and bone quality of T2DM mice was significantly 
      attenuated. All above results suggest that the HDAC1-Wnt/beta-Catenin signal axis is 
      involved in the anti-diabetic bone loss effect of exendin-4, and HDAC1 may be the 
      target of exendin-4.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Deng, Ying
AU  - Deng Y
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Zhu, Wenyi
AU  - Zhu W
AD  - Medical Department of Graduate School, Nanchang University, Nanchang, PR China.
FAU - Anhua Lin
AU  - Anhua Lin
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Wang, Chenxiu
AU  - Wang C
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Xiong, Changhui
AU  - Xiong C
AD  - Department of Science and Education, Jiangxi Provincial People(')s Hospital 
      Affiliated to Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Xu, Fanghua
AU  - Xu F
AD  - Pathology Department, Pingxiang People's Hospital of Southern Medical University, 
      Pingxiang, Jiangxi, 337055, PR China.
FAU - Li, Jinfeng
AU  - Li J
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Huang, Shuijin
AU  - Huang S
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Zhang, Na
AU  - Zhang N
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China.
FAU - Huo, Yanan
AU  - Huo Y
AD  - Endocrinology Department, Jiangxi Provincial People(')s Hospital Affiliated to 
      Nanchang University, Nanchang, Jiangxi, 330006, PR China. Electronic address: 
      13970029871@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210128
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Hypoglycemic Agents)
RN  - 9P1872D4OL (Exenatide)
RN  - EC 3.5.1.98 (Hdac1 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/*physiopathology
MH  - Disease Models, Animal
MH  - Exenatide/*pharmacology
MH  - Histone Deacetylase 1/*metabolism
MH  - Hypoglycemic Agents/pharmacology
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Osteogenesis/*drug effects
MH  - Wnt Signaling Pathway/*drug effects
OTO - NOTNLM
OT  - Bone loss
OT  - Exendin-4
OT  - HDAC1
OT  - Osteogenic differentiation
OT  - Type 2 diabetes mellitus
OT  - Wnt/beta-Catenin
COIS- Declaration of competing interest The authors declare that they have no competing 
      interests.
EDAT- 2021/02/01 06:00
MHDA- 2021/09/01 06:00
CRDT- 2021/01/31 20:27
PHST- 2020/11/08 00:00 [received]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/02/01 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2021/01/31 20:27 [entrez]
AID - S0006-291X(21)00074-7 [pii]
AID - 10.1016/j.bbrc.2021.01.039 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Mar 12;544:8-14. doi: 
      10.1016/j.bbrc.2021.01.039. Epub 2021 Jan 28.