ArticleBone2018
Pharmacological inhibition of tankyrase induces bone loss in mice by increasing osteoclastogenesis.
Article in Bone, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Disrupting the tumor-associated TNKS-USP25 protein-protein interface in cancer: structural basis, druggability, and therapeutic opportunities.RSC advances · 2026Review
- KRT17 promotes triple negative breast cancer through activation of Wnt signaling and γδ T-cells recruitment.Communications biology · 2026Article
- A First-In-Human Dose-Escalation Phase I Study of Basroparib, a Tankyrase Inhibitor, in Patients with Advanced-Stage Solid Tumors.Cancer research communications · 2025Article
- Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies.Bone research · 2025Article
- Tankyrase: a promising therapeutic target with pleiotropic action.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- The emerging era of personalized medicine in advanced colorectal cancer.Journal of gastroenterology and hepatology · 2022Review
- The Tankyrase Inhibitor OM-153 Demonstrates Antitumor Efficacy and a Therapeutic Window in Mouse Models.Cancer research communications · 2022Article
- TRAPS mutations inFrontiers in immunology · 2022Article
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies.International journal of molecular sciences · 2021Review
- Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines.iScience · 2021Article
- SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus.International journal of molecular sciences · 2021Article
- Crosstalk between adipocytes and M2 macrophages compensates for osteopenic phenotype in theExperimental biology and medicine (Maywood, N.J.) · 2021Article
- E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation.Frontiers in cell and developmental biology · 2021Review
- Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice.International journal of obesity (2005) · 2020Article
- WNT Signaling in Melanoma.International journal of molecular sciences · 2020Review
- Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor.Journal of medicinal chemistry · 2020Article
- Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis.International journal of molecular sciences · 2020Article
- RANKL-independent osteoclastogenesis in the SH3BP2 cherubism mice.Bone reports · 2020Article
- Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models.Communications biology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since tankyrase inhibitors suppress the degradation of AXIN protein, a negative regulator of the canonical Wnt pathway, they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are being investigated as drug candidates for cancer and fibrotic diseases, in which the Wnt pathways are aberrantly activated. Tankyrase is also reported to degrade the adaptor protein SH3BP2 (SH3 domain-binding protein 2). We have previously shown that SH3BP2 gain-of-function mutation enhances receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in murine bone marrow-derived macrophages (BMMs). Although the interaction between tankyrase and SH3BP2 has been reported, it is not clear whether and how the inhibition of tankyrase affects bone cells and bone mass. Here, we have demonstrated that tankyrase inhibitors (IWR-1, XAV939, and G007-LK) enhanced RANKL-induced osteoclast formation and function in murine BMMs and human peripheral blood mononuclear cells through the accumulation of SH3BP2, subsequent phosphorylation of SYK, and nuclear translocation of NFATc1. Tankyrase inhibitors also enhanced osteoblast differentiation and maturation, represented by increased expression of osteoblast-associated genes accompanied by the accumulation of SH3BP2 protein and enhanced nuclear translocation of ABL, TAZ, and Runx2 in primary osteoblasts. Most importantly, pharmacological inhibition of tankyrase in mice significantly decreased tibia and lumbar vertebrae bone volumes in association with increased numbers of osteoclasts. Our findings uncover the role of tankyrase inhibition in bone cells and highlight the potential adverse effects of the inhibitor on bone.
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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.