LRP5 Down‐Regulation Exacerbates Inflammation and Alveolar Bone Loss in Periodontitis by Inhibiting PI3K/c‐FOS Signalling

ABSTRACT Aim To investigate the involvement of low‐density lipoprotein receptor‐related protein 5 (LRP5) in inflammation and alveolar bone loss in periodontitis. Materials and Methods Gingival tissues were obtained from 10 periodontitis patients and 10 healthy individuals. Wild‐type (WT) and osteoblast‐specific Lrp5 conditional knock‐out C57BL/6 (LRP5fl/fl;Oc‐Cre) mice were used to establish a ligature‐induced mouse model of periodontitis. Human periodontal ligament stem cells (hPDLSCs) were isolated and used to further verify the mechanism through which LRP5 mediates periodontitis in vitro. Micro‐computed tomography, haematoxylin and eosin staining, immunohistochemistry, quantitative reverse‐transcription PCR, western blotting, enzyme‐linked immunosorbent assay and RNA sequencing were performed to explore the role of LRP5 in periodontitis and the underlying mechanism. Results LRP5 expression was down‐regulated in human/mouse periodontal tissues compared to that in healthy controls. Compared to those in wild‐type mice, the periodontal tissues of LRP5fl/fl;Oc‐Cre mice had increased alveolar bone loss, higher proinflammatory cytokine levels, and lower osteogenesis‐related factor expression. LRP5 expression was down‐regulated in hPDLSCs after lipopolysaccharide treatment in vitro. LRP5 knockdown increased proinflammatory cytokine production and inhibited osteoblastogenesis by inhibiting PI3K/c‐FOS signalling. Conclusion LRP5 down‐regulation exacerbates inflammation and alveolar bone loss in periodontitis by inhibiting PI3K/c‐FOS signalling, suggesting LRP5 as a potential therapeutic target for periodontitis.