The Regulatory Role Of Pdk1 In Periodontitis

Periodontitis, a chronic inflammatory disease, gradually undermines the structures that support the teeth, yet its underlying pathological mechanisms remain largely unclear. Pyruvate dehydrogenase kinase 1 (PDK1), a pivotal enzyme regulating glucose metabolism, has an unexplored role in periodontitis. To elucidate this role, we established a mouse model with a whole-body knockout of PDK1 for in vivo studies. Periodontitis was induced in these mice by ligating their second molars. For in vitro investigations, we manipulated PDK1 expression in RAW 264.7 cells through overexpression and knockout techniques. Furthermore, we assessed the effects of JX06, a specific inhibitor of PDK1, in a mouse model of periodontitis. Our in vivo studies revealed that PDK1 knockout exacerbated periodontal tissue destruction in mice. Conversely, administration of JX06 attenuated the progression of periodontitis. In vitro experiments demonstrated that PDK1 promoted osteoclast differentiation and associated mitochondrial dysfunction. In contrast, knockout of PDK1 inhibited these detrimental processes. Our findings indicate that PDK1 plays a detrimental role in the pathogenesis of periodontitis by enhancing osteoclast activity and mitochondrial dysfunction. These results suggest that PDK1 may represent a novel therapeutic target for the treatment of periodontitis.