ArticleOsteoarthritis and cartilage2016
Dickkopf-3 is upregulated in osteoarthritis and has a chondroprotective role.
Article in Osteoarthritis and cartilage, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Integrated analysis identifies conserved transcription factors TCF12, E2F1, and TEAD4 with diagnostic and therapeutic value in osteoarthritis subchondral bone.Genes & genomics · 2026Article
- Platelet-rich plasma in cartilage repair: biological mechanisms and clinical perspectives.Frontiers in sports and active living · 2026Review
- Dickkopf-3 enhances the chondroprotective effect of chondrogenic progenitor cells in a rat model of posttraumatic osteoarthritis.Journal of orthopaedic surgery and research · 2025Article
- Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis.eLife · 2024Article
- Potential use of stem cell therapies for treating osteoarthritis and rheumatoid arthritis.Annals of translational medicine · 2024Review
- Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.Frontiers in immunology · 2024Review
- The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.Cells · 2023Review
- Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.JCI insight · 2023Article
- The synovial environment steers cartilage deterioration and regeneration.Science advances · 2023Article
- Lineage-specific differences and regulatory networks governing human chondrocyte development.eLife · 2023Article
- Osteoarthritis: pathogenic signaling pathways and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Review
- The Wnt signaling cascade in the pathogenesis of osteoarthritis and related promising treatment strategies.Frontiers in physiology · 2022Review
- Dickkopf-3 (DKK3) Signaling in IL-1α-Challenged Chondrocytes: Involvement of the NF-κB Pathway.Cartilage · 2021Article
- Fetal Immunomodulatory Environment Following Cartilage Injury-The Key to CARTILAGE Regeneration?International journal of molecular sciences · 2021Article
- New Insights From Single-Cell Sequencing Data: Synovial Fibroblasts and Synovial Macrophages in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Critical Role of Synovial Tissue-Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation.Frontiers in immunology · 2021Review
- Comparison of two ASC-derived therapeutics in an in vitro OA model: secretome versus extracellular vesicles.Stem cell research & therapy · 2020Article
- Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models.Biology · 2020Review
- The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation.International journal of molecular medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveDickkopf-3 (Dkk3) is a non-canonical member of the Dkk family of Wnt antagonists and its upregulation has been reported in microarray analysis of cartilage from mouse models of osteoarthritis (OA). In this study we assessed Dkk3 expression in human OA cartilage to ascertain its potential role in chondrocyte signaling and cartilage maintenance.
methodsDkk3 expression was analysed in human adult OA cartilage and synovial tissues and during chondrogenesis of ATDC5 and human mesenchymal stem cells. The role of Dkk3 in cartilage maintenance was analysed by incubation of bovine and human cartilage explants with interleukin-1β (IL1β) and oncostatin-M (OSM). Dkk3 gene expression was measured in cartilage following murine hip avulsion. Whether Dkk3 influenced Wnt, TGFβ and activin cell signaling was assessed in primary human chondrocytes and SW1353 chondrosarcoma cells using qRT-PCR and luminescence assays.
resultsIncreased gene and protein levels of Dkk3 were detected in human OA cartilage, synovial tissue and synovial fluid. DKK3 gene expression was decreased during chondrogenesis of both ATDC5 cells and humans MSCs. Dkk3 inhibited IL1β and OSM-mediated proteoglycan loss from human and bovine cartilage explants and collagen loss from bovine cartilage explants. Cartilage DKK3 expression was decreased following hip avulsion injury. TGFβ signaling was enhanced by Dkk3 whilst Wnt3a and activin signaling were inhibited.
conclusionsWe provide evidence that Dkk3 is upregulated in OA and may have a protective effect on cartilage integrity by preventing proteoglycan loss and helping to restore OA-relevant signaling pathway activity. Targeting Dkk3 may be a novel approach in the treatment of OA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.