Abnormal circ-CDK8 expression affects periodontitis development by regulating let-7b-5p/MAP4K3 signaling

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Periodontology

Background:

• Periodontitis involves chronic inflammation and alveolar bone loss, hindering periodontal regeneration.
• Periodontal ligament stem cells (PDLSCs) are crucial for bone regeneration, but their osteogenic potential is compromised by inflammation.
• The role of circular RNAs (circRNAs) in regulating PDLSC differentiation under inflammatory conditions is not well understood.

Purpose of the Study:

• To investigate the role of circ-CDK8 in PDLSC differentiation during periodontitis.
• To elucidate the underlying mechanism involving the let-7b-5p/MAP4K3 pathway and autophagy.
• To identify circ-CDK8 as a potential therapeutic target for periodontal regeneration.

Main Methods:

• Analysis of circ-CDK8 expression in human periodontitis tissues versus healthy controls.
• In vitro inflammatory model using TNF-α and IL-1β stimulation of PDLSCs.
• Assessment of osteogenic differentiation and autophagy markers following circ-CDK8 manipulation.
• Mechanistic studies to confirm the let-7b-5p/MAP4K3 axis and autophagy modulation.

Main Results:

• Circ-CDK8 was significantly upregulated in periodontitis tissues.
• Suppression of circ-CDK8 in an inflammatory PDLSC model enhanced osteogenic differentiation.
• Circ-CDK8 inhibition reduced autophagic activity.
• The let-7b-5p/MAP4K3 pathway was identified as the mechanism through which circ-CDK8 regulates osteogenic differentiation and autophagy.

Conclusions:

• Circ-CDK8 plays a critical role in impairing PDLSC osteogenic differentiation under inflammatory conditions.
• The circ-CDK8/let-7b-5p/MAP4K3 pathway modulates autophagy to regulate bone regeneration in periodontitis.
• Circ-CDK8 represents a promising therapeutic target for enhancing periodontal regeneration.