PMID- 31432117
OWN - NLM
STAT- MEDLINE
DCOM- 20200204
LR  - 20200828
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 20
IP  - 4
DP  - 2019 Oct
TI  - Lentiviral‑mediated Shh reverses the adverse effects of high glucose on 
      osteoblast function and promotes bone formation via Sonic hedgehog signaling.
PG  - 3265-3275
LID - 10.3892/mmr.2019.10540 [doi]
AB  - Patients with diabetes tend to have an increased incidence of osteoporosis, which 
      may be associated with hyperglycemia; however, the pathogenic mechanisms 
      governing this interaction remain unknown. The present study sought to 
      investigate whether elevated extracellular glucose levels of bone mesenchymal 
      stem cells (BMSCs) could influence osteoblastic differentiation and whether the 
      intracellular Sonic hedgehog (Shh) pathway could adjust the effects. Furthermore, 
      to verify the results in vivo, a rat tooth extraction model was constructed. 
      BMSCs were incubated in eight types of culture medium, including low 
      glucose (LG), LG + lentivirus (Lenti), LG + Lenti‑small interfering RNA 
      (Lenti‑siRNA), LG + Lenti‑Shh, high glucose (HG), HG + Lenti, HG + Lenti‑siRNA 
      and HG + Lenti‑Shh. The lentiviral transfection efficiency was observed using a 
      fluorescence microscope; protein and mRNA expression was detected by western 
      blotting and reverse transcription‑quantitative polymerase chain reaction 
      (RT‑qPCR). The matrix mineralization and alkaline phosphatase (ALP) activity of 
      BMSCs were examined by Alizarin red staining and ALP activity assays, 
      respectively. The expression of osteogenesis‑related genes in BMSCs were 
      quantified by RT‑qPCR. The alveolar ridge reduction was measured and histological 
      sections were used to evaluate new bone formation in the tooth socket. With high 
      concentrations of glucose, Shh expression, matrix mineralization nodules 
      formation, ALP activity and the levels of bone morphogenic protein 4 (BMP4), bone 
      sialoprotein (BSP) and osteopontin (OPN) expression were greatly reduced compared 
      with LG and corresponding control groups. Whereas activated Shh signaling via 
      Lenti‑Shh could increase the number of matrix mineralization nodules, ALP 
      activity, and the expression levels of BMP4, BSP and OPN in BMSCs. Additionally, 
      in vivo assays demonstrated that Lenti‑Shh induced additional bone formation. 
      Collectively, the results of the present study indicated that HG inhibited the 
      Shh pathway in osteoblasts and resulted in patterning defects during osteoblastic 
      differentiation and bone formation, while the activation of Shh signaling could 
      suppress these deleterious effects.
FAU - Jiang, Zhu-Ling
AU  - Jiang ZL
AD  - Department of Implantology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Jin, Han
AU  - Jin H
AD  - Institute of Hard Tissue Development and Regeneration, The Second Affiliated 
      Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Liu, Zhong-Shuang
AU  - Liu ZS
AD  - Institute of Hard Tissue Development and Regeneration, The Second Affiliated 
      Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Liu, Ming-Yue
AU  - Liu MY
AD  - Department of Dentistry, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Cao, Xiao-Fang
AU  - Cao XF
AD  - Department of Dentistry, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Jiang, Yang-Yang
AU  - Jiang YY
AD  - Department of Dentistry, The Affiliated Hospital, Harbin Institute of Technology, 
      Harbin, Heilongjiang 150001, P.R. China.
FAU - Bai, Hong-Dan
AU  - Bai HD
AD  - Feiyang Dental Clinic, Heihe, Heilongjiang 164300, P.R. China.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Institute of Hard Tissue Development and Regeneration, The Second Affiliated 
      Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
FAU - Li, Ying
AU  - Li Y
AD  - Institute of Hard Tissue Development and Regeneration, The Second Affiliated 
      Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190731
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Shh protein, rat)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Glucose/*pharmacology
MH  - Hedgehog Proteins/*biosynthesis/genetics
MH  - *Lentivirus
MH  - Male
MH  - Osteoblasts/*metabolism/pathology
MH  - Osteogenesis/*drug effects/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - Transduction, Genetic
PMC - PMC6755203
EDAT- 2019/08/23 06:00
MHDA- 2020/02/06 06:00
PMCR- 2019/07/31
CRDT- 2019/08/22 06:00
PHST- 2018/11/05 00:00 [received]
PHST- 2019/07/11 00:00 [accepted]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/08/22 06:00 [entrez]
PHST- 2019/07/31 00:00 [pmc-release]
AID - mmr-20-04-3265 [pii]
AID - 10.3892/mmr.2019.10540 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Oct;20(4):3265-3275. doi: 10.3892/mmr.2019.10540. Epub 2019 Jul 
      31.