Abstract
Background
To explore the role of two major inhibitors of Wnt signal pathway, Dickkopf-1(DKK-1) and Sclerostin (SOST), in the pathogenesis of juvenile idiopathic arthritis (JIA).
Methods
88 patients with JIA, which including 49 patients with enthesitis-related arthritis (ERA), 21 oligoarthritis (oJIA) and 18 polyarthritis (pJIA), and 36 age-and sex-matched children as healthy controls (HC) were enrolled in this study. The plasma levels of DKK-1 and SOST, measured using commercially available ELISA kits, were analyzed the correlation between the levels of DKK-1/SOST and JIA, and were analyzed in 14 patients with JIA during before and after treatment.
Results
Plasma levels of DKK-1 were significantly higher in the patients with JIA than that in HC, the elevation of DKK-1 level was positively correlated with HLA-B27 positive JIA. DKK-1 levels dropped significantly in patient with JIA after treatment (P < 0.05). There was no significant change in SOST levels among different subtypes of JIA, patients with JIA during before and after treatment, and HC.
Conclusion
It was suggested that the DKK-1 may have a certain correlation with the pathogenesis of JIA, and DKK-1 levels are more closely related to the HLA-B27 positive-ERA.
Impact
-
The abnormally elevated levels of Dickkopf-1 (DKK-1) may be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). DKK-1 levels were more closely related to the HLA-B27 positive-enthesitis-related arthritis (ERA). DKK-1 is an inhibitor of Wnt signaling pathway that promotes osteoblastic new bone formation; it is very rare for pediatric patients with HLA-B27 positive-ERA to manifest typical spondylitis, while sacroiliac arthritis is relatively common, which may be related to the high levels of DKK-1, which is consistent with the early stage of ankylosing spondylitis (AS).
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Data availability
All data generated or analysed during this study are included in this published article.
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Acknowledgements
The authors would like to thank all the children and their parents for their generous and enthusiastic assistance during the phase of data collection. Besides, the contribution of Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine in recording data is heartfeltly appreciated.
Funding
Shanghai Municipal Health Planning Committee Project (201740233).
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L.Y. carried out the ELISA experiment, analyzed the data, and drafted the manuscript. J.W. designed and participated in experiments. H.H., F.D., X.X., C.L., and S.B. helped with coordination. Y.J. and J.W. conceived the study, designed and participated in experiments, and revised the manuscript. All authors have read and approved the final manuscript.
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Ye, L., Jin, Y., Huang, H. et al. The plasma levels of Dickkopf-1 elevated in patients with Juvenile Idiopathic Arthritis. Pediatr Res 94, 1349–1354 (2023). https://doi.org/10.1038/s41390-023-02637-8
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DOI: https://doi.org/10.1038/s41390-023-02637-8