PMID- 26782642
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20181113
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 37
IP  - 3
DP  - 2016 Mar
TI  - Bradykinin receptors and EphB2/EphrinB2 pathway in response to high 
      glucose-induced osteoblast dysfunction and hyperglycemia-induced bone 
      deterioration in mice.
PG  - 565-74
LID - 10.3892/ijmm.2016.2457 [doi]
AB  - This study was carried out in order to investigate bone dysfunction and the 
      involvement of bradykinin receptors and the Eph/Ephrin signaling pathway in 
      osteoblasts and in mice with diabetes-related osteoporosis in response to 
      exposure to high glucose. Osteogenic transdifferentiation was inhibited when the 
      osteoblasts were exposed to high glucose, and the expression levels of bone 
      formation-related genes [Runx2 and alkaline phosphatase (ALP)] were decreased, 
      while those of bone resorption-related genes [matrix metalloproteinase (MMP)9 and 
      carbonic anhydrase II (CAII)] were increased. Moreover, the mRNA and protein 
      expression levels of bradykinin receptor B1 (BK1R)/bradykinin receptor B2 (BK2R) 
      and EphB2/EphrinB2 were significantly decreased in the osteoblasts following 
      exposure to high glucose. Intriguingly, the interaction between BK2R and 
      EphB2/EphrinB2 was confirmed, and BK2R loss-of-function significantly decreased 
      the mRNA and protein expression levels of EphB2/EphrinB4. In vivo, hyperglycemia 
      induced the disequilibrium of calcium homeostasis through the inhibition of bone 
      formation and the acceleration of bone resorption, which was manifested by the 
      reduction of trabecular bone mass of the primary and secondary spongiosa, as well 
      as by the increase in the number of mature osteoclasts throughout the proximal 
      tibial metaphysis in mice with diabetes-related osteoporosis. Furthermore, the 
      mRNA and protein expression levels of BK1R/BK2R and EphB2/EphrinB2 in the tibias 
      of the mice with diabetes-related osteoporosis were significantly decreased. 
      These results demonstrate that bradykinin receptors and the EphB4/EphrinB2 
      pathway mediate the development of complications in mice with diabetes-related 
      osteoporosis and suggest that the inactivation of bradykinin receptors and the 
      EphB4/EphrinB2 pathway enhance the severity of complications in mice with 
      diabetes-related osteoporosis.
FAU - Wu, Min
AU  - Wu M
AD  - Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Ai, Wenting
AU  - Ai W
AD  - Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 
      710068, P.R. China.
FAU - Chen, Lin
AU  - Chen L
AD  - Department of Pathology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 
      710068, P.R. China.
FAU - Zhao, Sihai
AU  - Zhao S
AD  - Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, 
      Shaanxi 710061, P.R. China.
FAU - Liu, Enqi
AU  - Liu E
AD  - Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, 
      Shaanxi 710061, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160112
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Ephrin-B2)
RN  - 0 (Receptors, Bradykinin)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.10.1 (Receptor, EphB2)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
EIN - Int J Mol Med. 2019 Apr;43(4):1920. PMID: 30816429
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Calcium/blood/urine
MH  - Cell Line
MH  - Creatinine/blood/urine
MH  - Ephrin-B2/*metabolism
MH  - Flow Cytometry
MH  - Glucose/*pharmacology
MH  - Hyperglycemia/blood/complications/*physiopathology/urine
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteoblasts/*drug effects/metabolism
MH  - Receptor, EphB2/*metabolism
MH  - Receptors, Bradykinin/*metabolism
MH  - Signal Transduction/drug effects
PMC - PMC4771119
EDAT- 2016/01/20 06:00
MHDA- 2016/12/20 06:00
PMCR- 2016/01/12
CRDT- 2016/01/20 06:00
PHST- 2015/07/20 00:00 [received]
PHST- 2015/12/30 00:00 [accepted]
PHST- 2016/01/20 06:00 [entrez]
PHST- 2016/01/20 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
PHST- 2016/01/12 00:00 [pmc-release]
AID - ijmm-37-03-0565 [pii]
AID - 10.3892/ijmm.2016.2457 [doi]
PST - ppublish
SO  - Int J Mol Med. 2016 Mar;37(3):565-74. doi: 10.3892/ijmm.2016.2457. Epub 2016 Jan 
      12.