ArticleNature communications2019
Wwp2 maintains cartilage homeostasis through regulation of Adamts5.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Osteoarthritis in the Elderly Population: Preclinical Evidence of Nutrigenomic Activities of Flavonoids.Nutrients · 2023Pooled it
- Emerging therapies for knee osteoarthritis.Nature reviews. Rheumatology · 2026Review
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- A Human Accelerated Region Drives Opposing Heterochronic Changes in Craniofacial and Limb Development.bioRxiv : the preprint server for biology · 2026Article
- The Versatile Role of GDF5 in Chondrogenic Progenitor Cell-mediated Cartilage Regeneration via a Hyaluronic Acid-fibrin IPN Hydrogel Platform.Pharmaceutical research · 2026Article
- Targeting E3 Ubiquitin Ligases in Post-Traumatic Osteoarthritis: Therapeutic Opportunities and Pharmacological Perspectives.Pharmaceutics · 2026Review
- Proteomic aging clocks in epidemiological studies: advances, applications and prospects.Nature aging · 2026Review
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- Identification of Chondrocyte Stemness-Associated Biomarkers in Osteoarthritis Using Bioinformatics and Machine Learning Approaches.Journal of inflammation research · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Decoding the regulatory role of noncoding RNAs in biological and vascular calcification.Molecular biology reports · 2025Review
- Synovial joint cavitation during limb skeletogenesis entails Na/K-ATPase ion pump expression and osmoregulatory activity.Development (Cambridge, England) · 2025Article
- Spatio-temporal reconstruction of gene expression patterns in developing mice.Development (Cambridge, England) · 2025Article
- Long-read sequencing of 945 Han individuals identifies structural variants associated with phenotypic diversity and disease susceptibility.Nature communications · 2025Article
- Molecular basis of individual locomotor function: Integrated understanding of gene expression regulation in the development and homeostasis of the musculoskeletal system.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- The multifaceted roles of E3 ubiquitin ligases in osteoarthritis.Frontiers in cell and developmental biology · 2025Review
- Ubiquitination and deubiquitination: Implications for the pathogenesis and treatment of osteoarthritis.Journal of orthopaedic translation · 2024Review
- Article
- The role of WWP1 and WWP2 in bone/cartilage development and diseases.Molecular and cellular biochemistry · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The WW domain-containing protein 2 (Wwp2) gene, the host gene of miR-140, codes for the Wwp2 protein, which is an HECT-type E3 ubiquitin ligases abundantly expressed in articular cartilage. However, its function remains unclear. Here, we show that mice lacking Wwp2 and mice in which the Wwp2 E3 enzyme is inactivated (Wwp2-C838A) exhibit aggravated spontaneous and surgically induced osteoarthritis (OA). Consistent with this phenotype, WWP2 expression level is downregulated in human OA cartilage. We also identify Runx2 as a Wwp2 substrate and Adamts5 as a target gene, as similar as miR-140. Analysis of Wwp2-C838A mice shows that loss of Wwp2 E3 ligase activity results in upregulation of Runx2-Adamts5 signaling in articular cartilage. Furthermore, in vitro transcribed Wwp2 mRNA injection into mouse joints reduces the severity of experimental OA. We propose that Wwp2 has a role in protecting cartilage from OA by suppressing Runx2-induced Adamts5 via Runx2 poly-ubiquitination and degradation.
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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.