ArticleStem cells (Dayton, Ohio)2011
Tumor necrosis factor inhibits mesenchymal stem cell differentiation into osteoblasts via the ubiquitin E3 ligase Wwp1.
Article in Stem cells (Dayton, Ohio), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 148 citations in OpenAlex.
- Low-Intensity Pulsed Ultrasound Enhances Intramembranous Bone Healing in a Critical-Size Bone Defect of the Rat Calvaria.Journal of clinical medicine · 2026Article
- Targeting WWP1 ameliorates osteoarthritis by suppressing KLF15 ubiquitination to restore mtDNA and mitochondrial function.Molecular genetics and genomics : MGG · 2026Article
- Non-enzymatic function of QSOX2 directly regulates the JUNB-ITGB4 axis and enhanced resistance to osimertinib in EGFR-mutation lung adenocarcinoma.Cell death discovery · 2026Article
- piR-27222 alleviates dexamethasone-induced osteoporosis by inhibiting ferroptosis through modulating WWP1.Journal of orthopaedic surgery and research · 2026Article
- SIAH1-Mediated Ubiquitination and Degradation of TRIB3 Modulate Osteogenic and Adipogenic Differentiation.Stem cells international · 2026Article
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Role of Cytokines in Bone Diseases and Their Therapeutic Application.ImmunoTargets and therapy · 2026Review
- Biomaterial-mediated macrophage polarization remodeling and sequential regulation: a potential strategy in bone infections treatment.Bone research · 2025Review
- WW Domain-Containing E3 Ubiquitin Protein Ligase 1 (WWP1) as a Factor in Obesity-Related Metabolic Disorders: Emerging Molecular Mechanisms in Metabolic Tissues.International journal of molecular sciences · 2025Review
- TNF reduces osteogenic cell fate in PDL cells at transcriptional and functional levels without alteration of periodontal proliferative capacity.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2025Article
- Priming of mouse pre-osteoblasts with Interleukin-3 attenuates TNF-α-induced-inhibition of osteoblast differentiation.BMC musculoskeletal disorders · 2025Article
- Ketogenic diet and β-hydroxybutyrate in osteoporosis: current progress and controversy.Frontiers in nutrition · 2025Review
- Osteosarcopenia: epidemiology, molecular mechanisms, and management.Frontiers in endocrinology · 2025Review
- Impact of Different Cell Types on the Osteogenic Differentiation Process of Mesenchymal Stem Cells.Stem cells international · 2025Review
- The role of WWP1 and WWP2 in bone/cartilage development and diseases.Molecular and cellular biochemistry · 2024Review
- CRISPR-mediated Sox9 activation and RelA inhibition enhance cell therapy for osteoarthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- Tumour necrosis factor α regulates the miR-27a-3p-Sfrp1 axis in a mouse model of osteoporosis.Experimental physiology · 2024Article
- Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints.Nature communications · 2024Article
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with chronic inflammatory disorders, such as rheumatoid arthritis, often have osteoporosis due to a combination of Tumor necrosis factor-induced increased bone resorption and reduced bone formation. To test if TNF inhibits bone formation by affecting the commitment and differentiation of mesenchymal stem cells (MSCs) into osteoblasts, we examined the osteogenic potential of MSCs from TNF transgenic (TNF-Tg) mice, a model of chronic inflammatory arthritis. MSC-enriched cells were isolated from bone marrow stromal cells using negative selection with anti-CD45 antibody coated magnetic beads. The expression profile of MSC surface markers the osteogenic, chondrogenic, and adipogenic properties of CD45(-) cells were confirmed by FACS and cell differentiation assays. MSC-enriched CD45(-) cells from TNF-Tg mice formed significantly decreased numbers of fibroblast and ALP(+) colonies and had a decreased expression of osteoblast marker genes. As TNF may upregulate ubiquitin ligases, which negatively regulate osteoblast differentiation, we examined the expression levels of several ubiquitin ligases and found that Wwp1 expression was significantly increased in MSC-enriched CD45(-) cells of TNF-Tg mice. Wwp1 knockdown rescued impaired osteoblast differentiation of TNF-Tg CD45(-) cells. Wwp1 promotes ubiquitination and degradation of JunB, an AP-1 transcription factor that positively regulates osteoblast differentiation. Injection of TNF into wild-type mice resulted in decreased osteoblast differentiation of MSCs and increased JunB ubiquitination, which was completely blocked in Wwp1(-/-) mice. Thus, Wwp1 targets JunB for ubiquitination and degradation in MSCs after chronic exposure to TNF, and inhibition of Wwp1 in MSCs could be a new mechanism to limit inflammation-mediated osteoporosis by promoting their differentiation into osteoblasts.
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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.