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

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.