ArticleClinical rheumatology2021
Dickkopf-1 perpetuated synovial fibroblast activation and synovial angiogenesis in rheumatoid arthritis.
Article in Clinical rheumatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- New Cardiovascular Risk Biomarkers in Rheumatoid Arthritis: Implications and Clinical Utility-A Narrative Review.Biomedicines · 2025Review
- DKK-1 and Its Influences on Bone Destruction: A Comparative Study in Collagen-Induced Arthritis Mice and Rheumatoid Arthritis Patients.Inflammation · 2024Article
- Cell Cultures as a Versatile Tool in the Research and Treatment of Autoimmune Connective Tissue Diseases.Cells · 2023Review
- Review
- Dkk-1-TNF-α crosstalk regulates MC3T3E1 pre-osteoblast proliferation and differentiation under mechanical stress through the ERK signaling pathway.Molecular and cellular biochemistry · 2023Article
- Conditioned Medium - Is it an Undervalued Lab Waste with the Potential for Osteoarthritis Management?Stem cell reviews and reports · 2023Review
- Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes.International journal of molecular sciences · 2022Article
- Effects of Biological/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis.International journal of molecular sciences · 2022Review
- Melanocortin therapies to resolve fibroblast-mediated diseases.Frontiers in immunology · 2022Review
- STAT6 Blockade AbrogatesFrontiers in immunology · 2022Article
- Tail suspension delays ectopic ossification in proteoglycan-induced ankylosing spondylitis in mice via miR-103/DKK1.Experimental and therapeutic medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveDickkopf-1 (Dkk-1), a regulatory molecule of the Wnt pathway, is elevated and leads to bone resorption in patients with RA. This study is aimed to investigate the contribution of Dkk-1 to synovial inflammation and synovial fibroblast-mediated angiogenesis in RA.
methodsThe expression of Dkk-1 in RA synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF) was detected by real-time PCR and ELISA, respectively. RASF were stimulated with different pro-inflammatory factors. The expression of angiogenic factors, pro-inflammatory cytokines, and MMPs in RASF was analyzed by real-time PCR when Dkk-1 was inhibited or overexpressed. Meanwhile, the concentrations of MCP-1, IL-6, IL-8, and MMP-3 in the cell culture supernatant were assessed by ELISA. The effects of Dkk-1 on the MAPK signaling pathway were evaluated by western blot. Matrigel tube formation assay was employed to reveal the direct and indirect effects of Dkk-1 on synovial angiogenesis.
resultsDkk-1 expression was elevated in synovial fluids and synovial fibroblasts of RA patients. Treatment with various pro-inflammatory cytokines significantly promoted DKK-1 expression in RASF. The production of potent angiogenic factors, pro-inflammatory cytokines, and MMPs in RASF was elevated, whereas the reverse results were found in the inhibitor groups. Silenced Dkk-1expression in RASF dampened capillary tube organization in both direct and indirect manners, resulting in restrained ERK, JNK, and p38 signaling pathway activation.
conclusionWe concluded that Dkk-1 exacerbated the inflammation, cartilage erosion, and angiogenesis mediated by synovial fibroblasts in RA. Modulation of DKK-1 expression may facilitate development of novel strategies to control RA. Key points • Dkk-1 expression was elevated in synovial fluids and synovial fibroblasts of RA patients. • Treatment with various pro-inflammatory cytokines significantly promoted DKK-1 expression. • Silenced Dkk-1expression in RASF dampened capillary tube organization.
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