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Mechanical Force Modulates Alveolar Bone Marrow Mesenchymal Cells Characteristics for Bone Remodeling during Orthodontic Tooth Movement through Lactate Production

Orthodontic tooth movement (OTM) relies on mechanical force-induced bone remodeling. As a metabolic intermediate of glycolysis, lactate has recently been discovered to participate in bone remodeling by serving as a signaling molecule. However, whether lactate could respond to mechanical stimulus during OTM, as well as whether lactate has an impact on the alveolar bone remodeling during orthodontics, remain to be further elucidated. In the current study, we observed physiologically elevated production of lactate along with increased osteogenic differentiation, proliferation, and migration of alveolar bone marrow mesenchymal cells (ABMMCs) under mechanical force. Inhibition of lactate, induced by cyclic mechanical stretch by GNE-140, remarkably suppressed the osteogenic differentiation, proliferation, and migration, yet enhanced apoptosis of ABMMCs. Mechanistically, these regulatory effects of lactate were mediated by histone lactylation. Taken together, our results suggest that force-induced lactate is involved in controlling bone remodeling-related cellular activities in ABMMCs and plays a vital role in the alveolar bone remodeling during OTM. Our findings indicate that lactate might be a critical modulator for alveolar bone remodeling during OTM, providing a novel therapeutic target for the purpose of more effectively controlling tooth movement and improving the stability of orthodontic results.

 

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The study described in this passage suggests that lactate, a metabolic intermediate of glycolysis, plays a significant role in bone remodeling during orthodontic tooth movement (OTM). The researchers found that mechanical force induces elevated lactate production, which leads to increased osteogenic differentiation, proliferation, and migration of alveolar bone marrow mesenchymal cells (ABMMCs).

The researchers also observed that inhibiting lactate production using GNE-140 resulted in a significant reduction in osteogenic differentiation, proliferation, and migration, and an increase in apoptosis of ABMMCs. These effects were mediated by histone lactylation, indicating that lactate controls bone remodeling-related cellular activities in ABMMCs.

The findings of this study suggest that lactate may be a critical modulator of alveolar bone remodeling during OTM and could be a potential therapeutic target for improving the stability of orthodontic results. The results of this study have important implications for the development of new treatment strategies for orthodontic patients.

Related Products

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S6675 (R)-GNE-140 (R)-GNE-140 is a selective inhibitor of the LDHA and LDHB with IC50s of 3 nM and 5 nM, respectively. The R enantiomer of GNE-140 is 18-fold more potent than S enantiomer.

Related Targets

LDH Dehydrogenase