KDM6B/Pdk1 glycolytic pathway-driven ZEB2 lactylation promotes cellular cementum formation
Zhengkun Yang1, Huiyi Wang1,2, Junhong Xiao1,3
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine, Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Researchers discovered a new pathway involving KDM6B, PDK1, and ZEB2 lactylation that is crucial for cementum regeneration. This finding offers novel strategies for treating periodontitis and restoring lost teeth.
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Dental Research
Background:
- Periodontitis causes irreversible tooth loss due to cementum deterioration.
- Cementum regeneration is vital for periodontal repair.
- Understanding cementum formation mechanisms can inform regenerative strategies.
Purpose of the Study:
- To identify key molecular regulators of cementoblast mineralization and formation.
- To elucidate the role of lysine demethylase 6B (KDM6B) in cementogenesis.
- To explore the KDM6B-mediated metabolic pathways influencing cementum regeneration.
Main Methods:
- Seahorse assay to analyze cellular metabolism.
- Chromatin Immunoprecipitation (ChIP) and RNA sequencing to identify gene targets.
- In vitro and in vivo experiments to validate findings.
- Assessment of cementoblast mineralization and formation.
Main Results:
- KDM6B was identified as a positive regulator of cementoblast mineralization.
- KDM6B regulates glycometabolic reprogramming, targeting pyruvate dehydrogenase kinase 1 (PDK1).
- The KDM6B-PDK1 axis promotes ZEB2 lactylation, enhancing cementoblast mineralization.
- Sodium lactate supplementation rescued mineralization defects.
Conclusions:
- The KDM6B-PDK1-ZEB2 lactylation axis is essential for cementogenesis.
- This pathway provides new insights into periodontal regeneration.
- Targeting this axis may offer therapeutic potential for periodontitis treatment.
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