Glycometabolic reprogramming in cementoblasts: A vital target for enhancing cell mineralization

Area of Science:

• Periodontology
• Cellular Metabolism
• Biomineralization

Background:

• Cementum, a key periodontal tissue, attaches teeth to bone and protects the root surface.
• Cementoblasts are vital for periodontal tissue restoration, similar to osteoblasts.
• Glucose metabolism's role in bone remodeling is known, but cementoblast metabolism is poorly understood.

Purpose of the Study:

• To investigate the glucose metabolism and bioenergetic pathways in cementoblasts during mineralization.
• To elucidate the specific metabolic strategies employed by cementoblasts for tissue formation.

Main Methods:

• Immunohistochemistry and 18F-fluorodeoxyglucose (18F-FDG) in vivo tracing.
• Comparison of bioenergetic profiles between mineralized and unmineralized cementoblasts.
• RNA sequencing, targeted energy metabolomics, and Seahorse assays.
• Analysis of lactate dehydrogenase A (LDHA) function.

Main Results:

• Cementum formation showed significantly higher glucose metabolism.
• Mineralized cementoblasts exhibited increased glucose consumption and lactate production, with upregulated glycolysis and downregulated oxidative phosphorylation.
• Glycolytic metabolites were elevated in mineralized cementoblasts.
• Seahorse assays confirmed increased glycolytic flux and reduced oxygen consumption.
• Lactate dehydrogenase A (LDHA) was identified as a positive regulator of cementoblast mineralization.

Conclusions:

• Cementoblasts predominantly utilize glycolysis over oxidative phosphorylation during the mineralization process.
• This metabolic preference is critical for the adaptive and reparative functions of cementum.
• Understanding cementoblast bioenergetics offers insights into periodontal tissue maintenance and restoration.