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Alpha-ketoglutarate promotes alveolar bone regeneration by modulating M2 macrophage polarization

Authors :
Yuhan Li
Linfeng Liu
Yuyu Li
Wei Song
Bin Shao
Hanwen Li
Weimin Lin
Qiwen Li
Xinxing Shuai
Mingxuan Bai
Bin Zhao
Yuchen Guo
Quan Yuan
Yuan Wang
Source :
Bone Reports, Vol 18, Iss , Pp 101671- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Objectives: Alpha-ketoglutarate (αKG) is an essential metabolite that plays a crucial role in skeletal homeostasis. Here we aim to investigate the effect of αKG on alveolar socket healing and reveal the underlying mechanism in the view of macrophage polarization. Methods: In a murine model pretreated with or without αKG, mandibular first molars were extracted. Mandibular tissues were harvested for microCT and histological analyses. Immunofluorescence was used to evaluate macrophage polarization during healing process. Macrophages with αKG/vehicle supplementation in vitro were proceeded to quantitative real-time PCR and flow cytometry to further elucidate the mechanism. Results: MicroCT and histological analyses showed accelerated healing and enhanced bone regeneration of extraction sockets in experimental group. αKG increased new bone volume in alveolar sockets and promoted the activity of both osteoblastogenesis and osteoclastogenesis. αKG administration reduced M1 pro-inflammatory macrophages in an early phase and promoted anti-inflammatory M2 macrophage polarization in a later phase. Consistently, the expressions of M2 marker genes were augmented in αKG group, while M1 marker genes were downregulated. Flow cytometry revealed the increased ratio of M2/M1 macrophages in cells treated with αKG. Conclusions: αKG accelerates the healing process of extraction sockets via orchestrating macrophage activation, with promising therapeutic potential in oral clinics.

Details

Language :
English
ISSN :
23521872
Volume :
18
Issue :
101671-
Database :
Directory of Open Access Journals
Journal :
Bone Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.6eb0f0efbd749599b271478d886dec0
Document Type :
article
Full Text :
https://doi.org/10.1016/j.bonr.2023.101671