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Updated: Mar 28, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Dickkopf-3 is upregulated in osteoarthritis and has a chondroprotective role
S J B Snelling1, R K Davidson2, T E Swingler2
1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Objective:
Dickkopf-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.
Methods:
Dkk3 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.
Results:
Increased 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.
Conclusions:
We 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.
Insights
Dickkopf-3 (Dkk3) is upregulated in osteoarthritis (OA) cartilage and may protect cartilage by preventing proteoglycan loss. Targeting Dkk3 could be a new treatment for OA.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Dickkopf-3 (Dkk3), a Wnt antagonist, is upregulated in osteoarthritis (OA) cartilage.
- Its role in chondrocyte signaling and cartilage maintenance requires further investigation.
Purpose of the Study:
- To assess Dkk3 expression in human OA cartilage.
- To investigate Dkk3's role in chondrocyte signaling and cartilage maintenance.
Main Methods:
- Analyzed Dkk3 expression in human OA cartilage and synovial tissues.
- Studied Dkk3's role in cartilage maintenance using explant cultures stimulated with IL1β and OSM.
- Assessed Dkk3's influence on Wnt, TGFβ, and activin signaling pathways.
Main Results:
- Dkk3 levels were increased in human OA cartilage, synovial tissue, and fluid.
- Dkk3 inhibited IL1β and OSM-induced proteoglycan and collagen loss in cartilage explants.
- Dkk3 enhanced TGFβ signaling while inhibiting Wnt3a and activin signaling.
Conclusions:
- Dkk3 is upregulated in OA and appears to protect cartilage integrity.
- Dkk3 prevents proteoglycan loss and modulates OA-relevant signaling pathways.
- Targeting Dkk3 presents a potential novel therapeutic strategy for OA treatment.
