ArticleThe Journal of cell biology2011
WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways.
Article in The Journal of cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed.
- Quercetin ameliorates rheumatoid arthritis-associated bone erosion via inhibiting the Wnt3a/β-catenin signaling axis.Molecular biology reports · 2026Article
- Molecular Mechanisms of Chondrocyte Hypertrophy Mediated by Physical Cues and Therapeutic Strategies in Osteoarthritis.International journal of molecular sciences · 2026Review
- APOA4 Protects Chondrocytes and Modulates Wnt Signaling in Osteoarthritis.Journal of inflammation research · 2026Article
- Characterizing the Long Non-Coding RNA Profile of Endometrial Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Anti-Inflammatory Role in Osteoarthritis.International journal of molecular sciences · 2025Article
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- The Role of Wnt3a/β-Catenin/TCF7L2 Pathway in Diabetes and Cardiorenal Complications.Cardiorenal medicine · 2025Review
- Enhanced chondrogenic potential in GelMA-based 3D cartilage model via Wnt3a surface immobilization.Scientific reports · 2024Article
- Article
- Decreased expression of GEM in osteoarthritis cartilage regulates chondrogenic differentiation via Wnt/β-catenin signaling.Journal of orthopaedic surgery and research · 2023Article
- Effect of glycosaminoglycans with different degrees of sulfation on chondrogenesis.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2023Article
- "Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.Bioactive materials · 2023Article
- Notch Signaling Regulates the Chondrogenic Potential of Both Articular Chondrocytes and Their Progenitors During Expansion.Stem cells (Dayton, Ohio) · 2023Article
- Wnt signalling in the articular cartilage: A matter of balance.International journal of experimental pathology · 2023Review
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- A DLG1-ARHGAP31-CDC42 axis is essential for the intestinal stem cell response to fluctuating niche Wnt signaling.Cell stem cell · 2023Article
- Disease modification and symptom relief in osteoarthritis using a mutated GCP-2/CXCL6 chemokine.EMBO molecular medicine · 2023Article
- Role of Wnt signaling pathway in joint development and cartilage degeneration.Frontiers in cell and developmental biology · 2023Review
- An integrated in silico-in vitro approach for identifying therapeutic targets against osteoarthritis.BMC biology · 2022Article
- Wnt3a knockdown promotes collagen type II expression in rat chondrocytes.Experimental and therapeutic medicine · 2022Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Activation and disruption of Wnt/β-catenin signaling both result in cartilage breakdown via unknown mechanisms. Here we show that both WNT-3A and the Wnt inhibitor DKK1 induced de-differentiation of human articular chondrocytes through simultaneous activation of β-catenin-dependent and independent responses. WNT-3A activates both the β-catenin-dependent canonical pathway and the Ca(2+)/CaMKII noncanonical pathways, with distinct transcriptional targets. WNT-3A promotes cell proliferation and loss of expression of the chondrocyte markers COL2A1, Aggrecan, and SOX9; however, proliferation and AXIN2 up-regulation are downstream of the canonical pathway and are rescued by DKK1, whereas the loss of differentiation markers is CaMKII dependent. Finally, we showed that in chondrocytes, the Ca(2+)/CaMKII-dependent and β-catenin-dependent pathways are reciprocally inhibitory, thereby explaining why DKK1 can induce loss of differentiation through de-repression of the CaMKII pathway. We propose a novel model in which a single WNT can simultaneously activate different pathways with distinct and independent outcomes and with reciprocal regulation. This offers an opportunity for selective pharmacological targeting.
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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.