Bradykinin receptors and EphB2/EphrinB2 pathway in response to high glucose-induced osteoblast dysfunction and hyperglycemia-induced bone deterioration in mice

International Journal of Molecular Medicine
Min WuEnqi Liu

Abstract

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, ...Continue Reading

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Citations

Apr 25, 2014·PloS One·Jong-Ho ChaKyu-Won Kim
May 18, 2020·Journal of Bone and Mineral Metabolism·Yihan LiTao Chen
Oct 4, 2016·Endocrine·Marta CarnovaliMassimo Mariotti
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Methods Mentioned

BETA
gene knockout
enzyme-linked immunosorbent assay
PCR
electrophoresis
Infrared Imaging
transfection
co-immunoprecipitation

Software Mentioned

GraphPad Prism
CellQuest
Odyssey Application
GraphPad

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