ArticleEBioMedicine2015
Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone.Biomolecules · 2025Review
- USP26 Combats Age-Related Declines in Self-Renewal and Multipotent Differentiation of BMSC by Maintaining Mitochondrial Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- CYLD alleviates NLRP3 inflammasome-mediated pyroptosis in osteoporosis by deubiquitinating WNK1.Journal of orthopaedic surgery and research · 2024Article
- Novel Peritoneal Sclerosis Rat Model Developed by Administration of Bleomycin and Lansoprazole.International journal of molecular sciences · 2023Article
- Activated FGFR3 suppresses bone regeneration and bone mineralization in an ovariectomized mouse model.BMC musculoskeletal disorders · 2023Article
- Meclozine ameliorates bone mineralization and growth plate structure in a mouse model of X‑linked hypophosphatemia.Experimental and therapeutic medicine · 2023Article
- Efficacy of soluble lansoprazole-impregnated beta-tricalcium phosphate for bone regeneration.Scientific reports · 2022Article
- Mesenchymal stem cell extracellular vesicles-derived microRNA-194-5p delays the development of intervertebral disc degeneration by targeting TRAF6.Regenerative therapy · 2022Article
- E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration.Stem cells international · 2022Review
- Observational
- Highly Selective Activation of Heat Shock Protein 70 by Allosteric Regulation Provides an Insight into Efficient Neuroinflammation Inhibition.EBioMedicine · 2017Article
- Cancer: fundamentals behind pH targeting and the double-edged approach.OncoTargets and therapy · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6) and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD). Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation.
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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 Socratic graph.