Hexokinase 2‐mediated glycolysis promotes receptor activator of NF‐κB ligand expression in Porphyromonas gingivalis lipopolysaccharide‐treated osteoblasts

Abstract

Background: Glucose metabolism plays a pivotal role in sustaining the inflammatory response to microbial stimulation by providing sufficient energy in immune cells. The main purpose of our study was to explore whether hexokinase 2 (HK2)-mediated glycolysis affected the expression of receptor activator of NF-κB Ligand (RANKL) in Porphyromonas gingivalis lipopolysaccharide (P.gingivalis-LPS)-treated osteoblasts and evaluate the potential involvement of the AKT/PI3K pathway activation during HK2-mediated glycolysis.Methods: Primary mice osteoblasts were treated with P. gingivalis-LPS, whereas the HK2 inhibitor (Lonidamine, LND) and small interference RNA were used to restrain HK2 expression. Conditioned medium from osteoblasts was utilized for culturing osteoclast precursors. The mRNA and protein levels of genes involved in glycolysis and bone metabolism including RANKL and osteoprotegerin (OPG) were detected by real-time PCR and western blotting. HK2 and lactate levels were detected by ELISA. Tartrate-resistant acid phosphatase (TRAP) staining was utilized to assess osteoclast formation. The involvement of the AKT/PI3K pathway in osteoblasts was explored by Western blotting. Results: P. gingivalis-LPS enhanced HK2 expression along with rising glycolysis in osteoblasts. LND and HK2-knockdown decreased RANKL expression and the RANKL/OPG ratio in osteoblasts, leading to less osteoclast formation from osteoclast precursors as evidenced by TRAP staining, while the osteogenic potential and proliferation of osteoblasts were not affected by HK2-knockdown. Moreover, P. gingivalis-LPS activated the AKT/PI3K pathway, which could regulate HK2 and RANKL expression in osteoblasts.Conclusions: HK2-mediated glycolysis promoted RANKL in osteoblasts and enhanced osteoclast differentiation. Targeting glycolysis may provide novel therapeutic methods for reducing alveolar bone loss.

Administration of Porphyromonas Gingivalis in Pregnant Mice Enhances Glycolysis and Histone Lactylation/ADAM17 Leading to Cleft Palate in Offspring

“…On the other hand, numerous adverse outcomes in offspring, including metabolic disorders, have been associated with maternal P. gingivalis infection 12,13 . Moreover, prior studies suggested that P. gingivalis infection can trigger a metabolic shift from OXPHOS to glycolysis as an adaptation to stressful conditions 14,15 , which is opposite to the normal metabolic progression of palate development in our previous study 11 . We then wonder if P. gingivalis infection disrupts glucose metabolism will affect palatogenesis.…”