Increased Expression of Glutaminase in Osteoblasts Promotes Macrophage Recruitment in Periapical Lesions
Journal
Journal of Endodontics
Journal Volume
43
Journal Issue
4
Pages
602-608
Date Issued
2017
Author(s)
Hou K.-L.
Hong C.-Y.
EDDIE HSIANG HUA LAI
Wang J.-S.
Abstract
Introduction Recently, we have shown that tissue hypoxia stimulates the progression of periapical lesions by up-regulating glycolysis-dependent apoptosis of osteoblasts. Other facets of hypoxia-induced metabolic reprogramming in disease pathogenesis require further investigation. In this study, we examined the connection between hypoxia-augmented glutamine catabolism in osteoblasts and the development of periapical lesions. Methods Primary human osteoblasts were cultured under hypoxia. The expression of glutaminase 1 (GLS1) was examined using Western blot analysis. The production of glutamate was measured by colorimetric assay. Knockdown of GLS1 was performed with small interfering RNA technology. C-C motif chemokine ligand 2 (CCL2) secretion and chemotaxis of J774 macrophages were examined by enzyme-linked immunosorbent assay and transwell migration assay, respectively. In a rat model of induced periapical lesions, the relations between disease progression and osteoblastic expression of GLS1 or macrophage recruitment were studied. Results Hypoxia enhanced GLS1 expression and subsequent glutamate production in osteoblasts. Glutamate induced chemoattraction of macrophages by osteoblasts through up-regulation of CCL2 synthesis. Hypoxia promoted CCL2 secretion and macrophage recruitment through augmentation of glutaminolysis. Knockdown of GLS1 abolished hypoxia-induced effects. In rat periapical lesions, progressive bone resorption was significantly related to elevated GLS1 expression in osteoblasts and increased macrophage recruitment. Conclusions In addition to the rise in glycolytic activity, the progression of periapical lesions is also associated with enhanced glutamine catabolism in osteoblasts. GLS1 may be a potential therapeutic target in the management of periapical lesions. ? 2016 American Association of Endodontists
SDGs
Other Subjects
GLS1 protein, human; glutaminase; glutamine; animal; cell culture; disease exacerbation; enzymology; human; macrophage; metabolism; osteoblast; pathology; physiology; rat; Sprague Dawley rat; tooth periapical disease; Western blotting; Animals; Blotting, Western; Cells, Cultured; Disease Progression; Glutaminase; Glutamine; Humans; Macrophages; Osteoblasts; Periapical Periodontitis; Rats; Rats, Sprague-Dawley
Type
journal article