PMID- 29032198
OWN - NLM
STAT- MEDLINE
DCOM- 20171229
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 495
IP  - 1
DP  - 2018 Jan 1
TI  - Antagonism of cysteinyl leukot-riene receptor 1 (cysLT1R) by montelukast 
      regulates differentiation of MC3T3-E1 cells under overloaded mechanical 
      environment.
PG  - 995-1001
LID - S0006-291X(17)32021-1 [pii]
LID - 10.1016/j.bbrc.2017.10.051 [doi]
AB  - Long-term exposure to overloaded mechanical environment induces bone fatigue 
      damage symptoms and osteoblast damages. Montelukast is a selective cysteinyl 
      leukot-riene receptor 1 (cysLT1R) antagonist, which has been used for the 
      treatment of bronchial asthma in clinics. In the current study, we have 
      identified a novel pharmacological role of montelukast by finding that it has 
      protective properties against overload damage in osteoblastic MC3T3-E1 cells. 
      Firstly, our results show that CysLT1R is expressed in MC3T3-E1 cells. Mechanical 
      tensile strain of 5000-7000 muepsilon resulted in a significant upregulation of CysLT1R 
      in osteoblastic MC3T3-E1 cells in an intensity dependent manner. Secondly, MTT 
      assay indicates that loading with 5000 muepsilon mechanical strain inhibited cell 
      proliferation, which was suppressed by montelukast treatment. Furthermore, 
      montelukast promotes cell differentiation by increasing the expression of ALP and 
      RUNX2. Alizarin Red S staining assay showed that montelukast abolished the 
      inhibitory effects of overload mechanics on osteoblast mineralization. 
      Mechanistically, the effect of montelukast on osteoblastic differentiation acted 
      by activating the extracellular regulated protein kinases (ERK) pathway. The 
      obtained results suggested that montelukast promotes proliferation and 
      differentiation in osteoblasts exposed to overload mechanics.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Wei, Jinsong
AU  - Wei J
AD  - Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang 524001, Guangdong, China. Electronic address: jlgdwei@163.com.
FAU - Chen, Siyuan
AU  - Chen S
AD  - Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang 524001, Guangdong, China.
FAU - Huang, Chengshuo
AU  - Huang C
AD  - Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang 524001, Guangdong, China.
FAU - Guo, Weixiong
AU  - Guo W
AD  - Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang 524001, Guangdong, China.
FAU - Yang, Shukai
AU  - Yang S
AD  - Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang 524001, Guangdong, China.
FAU - Feng, Bailin
AU  - Feng B
AD  - Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, 
      Zhanjiang 524001, Guangdong, China.
FAU - Chu, Jiaqi
AU  - Chu J
AD  - Department of Stem Cell Research and Cellular Therapy Center, Affiliated Hospital 
      of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China.
LA  - eng
PT  - Journal Article
DEP - 20171012
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Acetates)
RN  - 0 (Cyclopropanes)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Leukotriene)
RN  - 0 (Sulfides)
RN  - LRF7RW46ID (leukotriene D4 receptor)
RN  - MHM278SD3E (montelukast)
SB  - IM
MH  - 3T3 Cells
MH  - Acetates/*administration & dosage
MH  - Animals
MH  - Cell Differentiation/*physiology
MH  - Cyclopropanes
MH  - Gene Expression Regulation, Developmental/physiology
MH  - Leukotriene Antagonists/*administration & dosage
MH  - Mechanotransduction, Cellular/*physiology
MH  - Mice
MH  - Osteoblasts/cytology/drug effects/*physiology
MH  - Osteogenesis/*drug effects/physiology
MH  - Quinolines/*administration & dosage
MH  - Receptors, Leukotriene/drug effects/*metabolism
MH  - Stress, Mechanical
MH  - Sulfides
OTO - NOTNLM
OT  - Cysteinyl leukot-riene receptor 1
OT  - MC3T3-E1
OT  - Montelukast
OT  - Overload
EDAT- 2017/10/17 06:00
MHDA- 2017/12/30 06:00
CRDT- 2017/10/17 06:00
PHST- 2017/09/12 00:00 [received]
PHST- 2017/10/11 00:00 [accepted]
PHST- 2017/10/17 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
PHST- 2017/10/17 06:00 [entrez]
AID - S0006-291X(17)32021-1 [pii]
AID - 10.1016/j.bbrc.2017.10.051 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Jan 1;495(1):995-1001. doi: 
      10.1016/j.bbrc.2017.10.051. Epub 2017 Oct 12.