AI Article Synopsis
- α-Ketoglutarate (αKG) is important for bone healing and influences macrophage behavior during the healing process of alveolar sockets after tooth extraction.
- In studies with mice, treatment with αKG led to faster healing and greater bone regeneration compared to untreated subjects, as shown by microCT and histological analysis.
- αKG treatment resulted in a decrease of pro-inflammatory M1 macrophages early on, and an increase in anti-inflammatory M2 macrophages later, indicating a shift in macrophage polarization that supports healing.
Article 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 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 orchestrating macrophage activation, with promising therapeutic potential in oral clinics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064115 | PMC |
| http://dx.doi.org/10.1016/j.bonr.2023.101671 | DOI Listing |
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