PMID- 24786562
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20220129
IS  - 1365-2591 (Electronic)
IS  - 0143-2885 (Linking)
VI  - 48
IP  - 3
DP  - 2015 Mar
TI  - L-mimosine increases the production of vascular endothelial growth factor in 
      human tooth slice organ culture model.
PG  - 252-60
LID - 10.1111/iej.12307 [doi]
AB  - AIM: To assess the pro-angiogenic and pro-inflammatory capacity of the 
      dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine 
      in a tooth slice organ culture model. METHODOLOGY: Human teeth were sectioned 
      transversely into 600-mum-thick slices and cultured in medium supplemented with 
      serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. 
      Pulps were subjected to viability measurements based on formazan formation in MTT 
      assays. In addition, histological evaluation of pulps was performed based on 
      haematoxylin and eosin staining. Culture supernatants were subjected to 
      immunoassays for vascular endothelial growth factor (VEGF) to determine the 
      pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to 
      assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory 
      control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha 
      activity. Data were analysed using Student's t-test and Mann-Whitney U test. 
      RESULTS: Pulps within tooth slices remained vital upon L-mimosine stimulation as 
      indicated by formazan formation and histological evaluation. L-mimosine increased 
      VEGF production when normalized to formazan formation in the pulp tissue of the 
      tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin 
      (P < 0.01). Changes in normalized IL-6 and IL-8 levels upon treatment with 
      L-mimosine did not reach the level of significance (P > 0.05), whilst treatment 
      with IL-1, which served as positive control, increased IL-6 (P < 0.05) and IL-8 
      levels (P < 0.05). CONCLUSIONS: The prolyl hydroxylase inhibitor L-mimosine 
      increased VEGF production via HIF-1 alpha in the tooth slice organ culture model 
      whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will 
      reveal if these in vitro effects translate into dental pulp regeneration.
CI  - (c) 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.
FAU - Trimmel, K
AU  - Trimmel K
AD  - Department of Oral Surgery, Medical University of Vienna, Vienna, Austria; 
      Austrian Cluster for Tissue Regeneration, Vienna, Austria.
FAU - Cvikl, B
AU  - Cvikl B
FAU - Muller, H-D
AU  - Muller HD
FAU - Nurnberger, S
AU  - Nurnberger S
FAU - Gruber, R
AU  - Gruber R
FAU - Moritz, A
AU  - Moritz A
FAU - Agis, H
AU  - Agis H
LA  - eng
GR  - J 3379/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140628
PL  - England
TA  - Int Endod J
JT  - International endodontic journal
JID - 8004996
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 500-44-7 (Mimosine)
RN  - 512-64-1 (Echinomycin)
MH  - Cell Survival/drug effects
MH  - Dental Pulp/*cytology
MH  - Echinomycin/pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors
MH  - Interleukin-1/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Mimosine/*pharmacology
MH  - Molar
MH  - Neovascularization, Physiologic/*drug effects
MH  - Organ Culture Techniques
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/metabolism
OTO - NOTNLM
OT  - angiogenesis
OT  - dental pulp
OT  - hypoxia-inducible factor-1 alpha
OT  - interleukin
OT  - prolyl hydroxylase inhibitors
OT  - vascular endothelial growth factor
EDAT- 2014/05/03 06:00
MHDA- 2016/12/15 06:00
CRDT- 2014/05/03 06:00
PHST- 2013/03/21 00:00 [received]
PHST- 2014/04/26 00:00 [accepted]
PHST- 2014/05/03 06:00 [entrez]
PHST- 2014/05/03 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1111/iej.12307 [doi]
PST - ppublish
SO  - Int Endod J. 2015 Mar;48(3):252-60. doi: 10.1111/iej.12307. Epub 2014 Jun 28.