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

Periodontitis, a chronic inflammatory disorder characterized by progressive alveolar bone loss, relies heavily on the osteogenic differentiation capacity of periodontal ligament stem cells for bone regeneration. While inflammatory conditions are known to impair this osteogenic potential, the specific regulatory mechanisms, particularly those involving circular RNAs, remain to be elucidated. This study was therefore conducted to investigate the functional role of circ-CDK8 in regulating periodontal ligament stem cells (PDLSCs) differentiation under inflammatory conditions and to elucidate its mechanism of action through the let-7b-5p/MAP4K3 pathway and associated autophagy processes. Our investigation revealed significant upregulation of circ-CDK8 in periodontitis tissues compared to healthy tissues. Using an inflammatory model with TNF-α and IL-1β stimulation, we demonstrated that circ-CDK8 suppression enhanced osteogenic differentiation while concurrently reducing autophagic activity. Mechanistic studies established that circ-CDK8 executes its regulatory function through the let-7b-5p/MAP4K3 axis, where its inhibition promotes osteogenic differentiation via autophagy modulation. These findings not only identify a novel circ-CDK8/let-7b-5p/MAP4K3 regulatory pathway in periodontitis pathogenesis but also position circ-CDK8 as a promising therapeutic target for periodontal regeneration.