ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2013
Ubiquitin E3 ligase Wwp1 negatively regulates osteoblast function by inhibiting osteoblast differentiation and migration.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Neddylation of NFATc1 and Runx2 regulates osteoclast-osteoblast balance and represents a dual-action therapeutic target for postmenopausal osteoporosis.Experimental & molecular medicine · 2026Article
- Identification and validation of an interaction between the E3 ubiquitin ligase WWP1 and the Transcriptional Co-Activator WBP2 in the human heart.Biology open · 2026Article
- siRNA Delivery via Cross-Linked Gelatin Microparticles Enables Targeted Modulation of Osteogenic-Vascular Cross-Talk: An Advanced Human 3D in Vitro Test System for Therapeutic siRNA.Advanced healthcare materials · 2026Article
- piR-27222 alleviates dexamethasone-induced osteoporosis by inhibiting ferroptosis through modulating WWP1.Journal of orthopaedic surgery and research · 2026Article
- Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal.Biological research · 2025Article
- NEDD4 family E3 ligases in osteoporosis: mechanisms and emerging potential therapeutic targets.Journal of orthopaedic surgery and research · 2025Review
- Article
- The role of WWP1 and WWP2 in bone/cartilage development and diseases.Molecular and cellular biochemistry · 2024Review
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- Portrait of WWP1: the current state in human cancer.Frontiers in cell and developmental biology · 2024Review
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- WWP1 E3 ligase at the crossroads of health and disease.Cell death & disease · 2023Review
- GATA4-activated lncRNA MALAT1 promotes osteogenic differentiation through inhibiting NEDD4-mediated RUNX1 degradation.Cell death discovery · 2023Article
- RNF4~RGMb~BMP6 axis required for osteogenic differentiation and cancer cell survival.Cell death & disease · 2022Article
- NEDD4 E3 Ligases: Functions and Mechanisms in Bone and Tooth.International journal of molecular sciences · 2022Review
- Genome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation.International journal of molecular sciences · 2022Article
- E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration.Stem cells international · 2022Review
- Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice.PloS one · 2022Article
- The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease.International journal of molecular sciences · 2021Review
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitin E3 ligase-mediated protein degradation promotes proteasomal degradation of key positive regulators of osteoblast functions. For example, the E3 ligases--SMAD-specific E3 ubiquitin protein ligase 1 (Smurf1), Itch, and WW domain-containing E3 ubiquitin protein ligase 1 (Wwp1)--promote degradation of Runt-related transcription factor 2 (Runx2), transcription factor jun-B (JunB), and chemokine (C-X-C) receptor type 4 (CXCR-4) proteins to inhibit their functions. However, the role of E3 ligases in age-associated bone loss is unknown. We found that the expression level of Wwp1, but not Smurf1 or Itch, was significantly increased in CD45-negative (CD45(-)) bone marrow-derived mesenchymal stem cells from 6-month-old and 12-month-old wild-type (WT) mice. Wwp1 knockout (Wwp1(-/-)) mice developed increased bone mass as they aged, associated with increased bone formation rates and normal bone resorption parameters. Bone marrow stromal cells (BMSCs) from Wwp1(-/-) mice formed increased numbers and areas of alkaline phosphatase(+) and Alizarin red(+) nodules and had increased migration potential toward chemokine (C-X-C motif) ligand 12 (CXCL12) gradients. Runx2, JunB, and CXCR-4 protein levels were significantly increased in Wwp1(-/-) BMSCs. Wwp1(-/-) BMSCs had increased amount of ubiquitinated JunB protein, but Runx2 ubiquitination was no change. Knocking down JunB in Wwp1(-/-) BMSCs returned Runx2 protein levels to that in WT cells. Thus, Wwp1 negatively regulates osteoblast functions by affecting both their migration and differentiation. Mechanisms designed to decrease Wwp1 levels in BMSCs may represent a new approach to prevent the decrease in osteoblastic bone formation associated with aging.
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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.