BMAL1‐downregulation drives PANoptosis and the osteogenic differentiation impairment of PDLSCs by ERK/AP‐1 signaling pathway

• DOI: 10.1002/jper.24-0497
• Publication Date: 2025-04-22T06:54:45Z
• Authors: Luxu Wang; Ting Liu; Weidong Zhang; Hongrui Liu; Yuping Qi; Minqi Li
• Keywords: Osteopontin; RUNX2

Abstract Background One strategy to delay bone loss in periodontitis involves maintaining the osteogenic differentiation function of periodontal ligament stem cells (PDLSCs). The core circadian gene BMAL1 influences fate mesenchymal and is essential for regulating pyroptosis, apoptosis, necroptosis. PANoptosis, a novel form programmed cell death, simultaneously activates all 3 pathways. This study focuses on role BMAL1, process impairment PDLSCs. Methods A mouse model was established evaluate expression factors. We stimulated PDLSCs with lipopolysaccharide (LPS) used Western blot detect PANoptosis‐related Osteogenic factors were assessed using real‐time quantitative polymerase chain reaction (RT‐qPCR), blot, alkaline phosphatase, alizarin red staining. ERK pathway proteins examined by immunofluorescence investigate how regulates PANoptosis under inflammatory conditions. Results Treatment LPS leads downregulation expression, which subsequently induces RIPK1‐PANoptosome‐mediated PDLSCs, impairing their function. Inhibition RIPK1‐PANoptosome Nec‐1S improved differentiation‐related genes proteins. Overexpression synthetic ligand SR1078 alleviated these detrimental effects. U0126 reduced its downstream target AP‐1, effectively reversing impact PANoptosis. Conclusions triggers leading impaired provides new insights into pathogenesis suggests targets prevention treatment. Plain language summary Periodontitis chronic condition oral cavity marked destruction attachment resorption alveolar bone. rhythm cells, playing crucial encompassing necroptosis, may play activity Our aims elucidate underlying relationship between found that treatment Notably, inhibition Mechanistic exploration revealed through ERK/AP‐1 signaling pathway. highlights potential therapeutic mitigating periodontitis.