Journal
JOURNAL OF RHEUMATIC DISEASES
Volume 28, Issue 4, Pages 216-224Publisher
KOREAN COLL RHEUMATOLOGY
DOI: 10.4078/jrd.2021.28.4.216
Keywords
Ankylosing spondylitis; Tumor necrosis factor; DKK1; Enthesis; Bone formation
Categories
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2019R1A2C2004214, 2020R1A2C1102386]
- National Research Foundation of Korea [2020R1A2C1102386] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
This study found that AS patients have higher serum DKK1 levels compared to healthy controls, and TNF treatment can promote bone formation and DKK1 expression in enthesis cells. TNF-induced NF-kappa B activation upregulates DKK1 transcription, leading to enhanced bone formation in AS patients. Overall, DKK1 expression induced by TNF may contribute to the bone formation seen in the progression of ankylosing spondylitis.
Objective. This study aimed to determine the serum Dickkopf 1 (DKK1) levels in ankylosing spondylitis (AS) patients and decipher the mechanism of tumor necrosis factor (TNF)-mediated DKK1 regulation in human AS enthesis cells. Methods. The sera were obtained from 103 patients with AS and 30 healthy controls (HCs). The enthesis of facet joints were obtained from 4 AS patients and 5 controls. The serum levels of DKK1 were measured using ELISA and compared between AS and HCs. The impact of TNF on DKK1 expression in human primary spinal enthesis cells was evaluated using various molecular biology techniques and bone formation indicators. Results. AS patients showed higher serum DKK1 levels than HCs after adjusting for age (917.4 [615.3 similar to 1,310.0] pg/mL vs. 826.2 [670.3 similar to 927.8] pg/mL, p = 0.043). TNF treatment promoted bone formation and DKK1 expression in both control enthesis cells and those of AS. This enhanced bone formation by TNF was pronounced in AS-enthesis than those of controls. Mechanically, TNF induced NF-kappa B activation upregulates the DKK1 transcript level. While, NF-kappa B inhibitor led to downregulate DKK1 expression in the enthesis. Besides, DKK1 overexpression promoted bone formation in enthesis. Conclusion. TNF induced DKK1 expression in the enthesis through NF-kappa B activation. TNF-induced DKK1 expression may play a bone formation in the radiologic progression of ankylosing spondylitis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available