4.5 Article

Wnt antagonist secreted frizzled-related protein I (sFRP1) may be involved in the osteogenic differentiation of periodontal ligament cells in chronic apical periodontitis

Journal

INTERNATIONAL ENDODONTIC JOURNAL
Volume 54, Issue 5, Pages 768-779

Publisher

WILEY
DOI: 10.1111/iej.13461

Keywords

bone formation; chronic apical periodontitis; secreted frizzled-related protein I; Wnt betacatenin signalling pathway

Funding

  1. National Natural Science Foundation of China (NSFC) [81300876, 81771063]

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The study investigates the role of sFRP1 in osteogenic differentiation of hPDLCs during inflammation. Results show that P. gingivalis LPS inhibited osteogenic markers and the Wnt/beta-catenin signaling pathway, while sFRP1 inhibitor reversed these effects. Animal experiment confirmed the inhibitory effect of sFRP1 inhibitor on bone loss. Modulation of Wnt signaling through sFRP1 inhibition may provide a new approach for treating chronic apical periodontitis.
Aim To explore the mechanism of secreted frizzled-related protein I (sFRP1) involvement in the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under inflammatory conditions. Methodology hPDLCs were cultured in an osteogenic differentiation-inducing medium (odi) and subjected to the stimulation of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) with or without the inhibition of sFRP1. Quantitative real-time polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay were carried out to evaluate the expression of osteogenic markers as well as the classic Wnt signalling pathway. Periapical periodontitis was induced in Wistar rats to further confirm the effect of sFRP1 inhibitor on bone loss in vivo. After the Shapiro-Wilk normality test, data were analysed by Student's paired t-test or one-way Anova test with a P value less than 0.05 as the level of statistical significance. Results Significantly decreased mRNA and protein expression of osteogenic markers were detected in hPDLCs treated with P. gingivalis LPS during osteogenic induction (P < 0.001). Increased expression of sFRP1 was observed (P < 0.01), whilst Wnt/beta-catenin signalling pathway was inhibited by the addition of P. gingivalis LPS (P < 0.01). After the addition of the sFRP1 inhibitor, the decrease of osteogenic markers (P < 0.05) and the inhibition of Wnt/beta-catenin signalling pathway (P < 0.05) were reversed significantly. The animal experiment further confirmed that the sFRP1 inhibitor significantly reduced bone loss of periapical lesions in vivo (P < 0.0001). Conclusions Wnt antagonist sFRP1 was involved in the osteogenic differentiation of hPDLCs under inflammation. Modulation of the Wnt/beta-catenin signalling pathway through the inhibition of sFRP1 may offer a new perspective on the treatment of chronic apical periodontitis.

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