PMID- 26296196
OWN - NLM
STAT- MEDLINE
DCOM- 20160510
LR  - 20220331
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 8
DP  - 2015
TI  - High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes in Rats Impacts 
      Osteogenesis and Wnt Signaling in Bone Marrow Stromal Cells.
PG  - e0136390
LID - 10.1371/journal.pone.0136390 [doi]
LID - e0136390
AB  - Bone regeneration disorders are a significant problem in patients with type 2 
      diabetes mellitus. Bone marrow stromal cells (BMSCs) are recognized as ideal seed 
      cells for tissue engineering because they can stimulate osteogenesis during bone 
      regeneration. Therefore, the aim of this study was to investigate the osteogenic 
      potential of BMSCs derived from type 2 diabetic rats and the pathogenic 
      characteristics of dysfunctional BMSCs that affect osteogenesis. BMSCs were 
      isolated from normal and high-fat diet+streptozotocin-induced type 2 diabetic 
      rats. Cell metabolic activity, alkaline phosphatase (ALP) activity, 
      mineralization and osteogenic gene expression were reduced in the type 2 diabetic 
      rat BMSCs. The expression levels of Wnt signaling genes, such as beta-catenin, 
      cyclin D1 and c-myc, were also significantly decreased in the type 2 diabetic rat 
      BMSCs, but the expression of GSK3beta remained unchanged. The derived BMSCs were 
      cultured on calcium phosphate cement (CPC) scaffolds and placed subcutaneously 
      into nude mice for eight weeks; they were detected at a low level in newly formed 
      bone. The osteogenic potential of the type 2 diabetic rat BMSCs was not impaired 
      by the culture environment, but it was impaired by inhibition of the Wnt 
      signaling pathway, likely due to an insufficient accumulation of beta-catenin rather 
      than because of GSK3beta stimulation. Using BMSCs derived from diabetic subjects 
      could offer an alternative method of regenerating bone together with the use of 
      supplementary growth factors to stimulate the Wnt signaling pathway.
FAU - Qian, Chao
AU  - Qian C
AD  - Department of Prosthodontics, School of Stomatology, Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of 
      Stomatology. Shanghai, 200011, People's Republic of China.
FAU - Zhu, Chenyuan
AU  - Zhu C
AD  - Department of Prosthodontics, School of Stomatology, Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of 
      Stomatology. Shanghai, 200011, People's Republic of China.
FAU - Yu, Weiqiang
AU  - Yu W
AD  - Department of Prosthodontics, School of Stomatology, Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of 
      Stomatology. Shanghai, 200011, People's Republic of China.
FAU - Jiang, Xinquan
AU  - Jiang X
AD  - Department of Prosthodontics, School of Stomatology, Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of 
      Stomatology. Shanghai, 200011, People's Republic of China.
FAU - Zhang, Fuqiang
AU  - Zhang F
AD  - Department of Prosthodontics, School of Stomatology, Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of 
      Stomatology. Shanghai, 200011, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150821
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Calcium Phosphates)
RN  - 0 (Ccnd1 protein, rat)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 136601-57-5 (Cyclin D1)
RN  - 5W494URQ81 (Streptozocin)
RN  - 97Z1WI3NDX (calcium phosphate)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/genetics/metabolism
MH  - Animals
MH  - Bone Marrow Cells/drug effects/*metabolism/pathology
MH  - Calcium Phosphates/chemistry
MH  - Cyclin D1/genetics/metabolism
MH  - Diabetes Mellitus, Experimental/chemically induced/genetics/*metabolism/pathology
MH  - Diabetes Mellitus, Type 2/genetics/metabolism/pathology
MH  - Diet, High-Fat/adverse effects
MH  - Gene Expression Regulation
MH  - Glycogen Synthase Kinase 3/genetics/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/drug effects/*metabolism/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Osteogenesis/*genetics
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-myc/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Streptozocin
MH  - Transplantation, Heterologous
MH  - Wnt Signaling Pathway
PMC - PMC4546646
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/08/22 06:00
MHDA- 2016/05/11 06:00
PMCR- 2015/08/21
CRDT- 2015/08/22 06:00
PHST- 2015/04/21 00:00 [received]
PHST- 2015/08/04 00:00 [accepted]
PHST- 2015/08/22 06:00 [entrez]
PHST- 2015/08/22 06:00 [pubmed]
PHST- 2016/05/11 06:00 [medline]
PHST- 2015/08/21 00:00 [pmc-release]
AID - PONE-D-15-17196 [pii]
AID - 10.1371/journal.pone.0136390 [doi]
PST - epublish
SO  - PLoS One. 2015 Aug 21;10(8):e0136390. doi: 10.1371/journal.pone.0136390. 
      eCollection 2015.