ArticleProceedings of the National Academy of Sciences of the United States of America2015
Osteopetrosis in TAK1-deficient mice owing to defective NF-κB and NOTCH signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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
28 citing papers in PubMed, 45 citations in OpenAlex.
- Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment.Journal of advanced research · 2025Article
- Intake of eggshell membrane enhances bone mass and suppresses bone marrow adiposity in normal growing rats.Bone reports · 2025Article
- DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.The Journal of clinical investigation · 2023Article
- ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle.The EMBO journal · 2022Article
- The Role of TAK1 in RANKL-Induced Osteoclastogenesis.Calcified tissue international · 2022Review
- Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1.Nature communications · 2022Article
- Review
- Regeneration of Damaged Tendon-Bone Junctions (Entheses)-TAK1 as a Potential Node Factor.International journal of molecular sciences · 2020Review
- Regulatory network mediated by RBP-J/NFATc1-miR182 controls inflammatory bone resorption.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Intrinsic Restriction of TNF-Mediated Inflammatory Osteoclastogenesis and Bone Resorption.Frontiers in endocrinology · 2020Review
- BMPRIA is required for osteogenic differentiation and RANKL expression in adult bone marrow mesenchymal stromal cells.Scientific reports · 2018Article
- AnJBMR plus · 2018Article
- TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation.The Journal of experimental medicine · 2018Article
- Article
- C/EBPα transcription factor is regulated by the RANK cytoplasmicThe Journal of biological chemistry · 2018Article
- Effect of TAK1 on osteogenic differentiation of mesenchymal stem cells by regulating BMP-2 via Wnt/β-catenin and MAPK pathway.Organogenesis · 2018Article
- Does TNF Promote or Restrain Osteoclastogenesis and Inflammatory Bone Resorption?Critical reviews in immunology · 2018Review
- NUMB maintains bone mass by promoting degradation of PTEN and GLI1 via ubiquitination in osteoblasts.Bone research · 2018Article
- Distinct roles of TRAF6 and TAK1 in the regulation of adipocyte survival, thermogenesis program, and high-fat diet-induced obesity.Oncotarget · 2017Article
- NUMBL Interacts with TAK1, TRAF6 and NEMO to Negatively Regulate NF-κB Signaling During Osteoclastogenesis.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The MAP kinase TGFβ-activated kinase (TAK1) plays a crucial role in physiologic and pathologic cellular functions including cell survival, differentiation, apoptosis, inflammation, and oncogenesis. However, the entire repertoire of its mechanism of action has not been elucidated. Here, we found that ablation of Tak1 in myeloid cells causes osteopetrosis in mice as a result of defective osteoclastogenesis. Mechanistically, Tak1 deficiency correlated with increased NUMB-like (NUMBL) levels. Accordingly, forced expression of Numbl abrogated osteoclastogenesis whereas its deletion partially restored osteoclastogenesis and reversed the phenotype of Tak1 deficiency. Tak1 deletion also down-regulated Notch intracellular domain (NICD), but increased the levels of the transcription factor recombinant recognition sequence binding protein at Jκ site (RBPJ), consistent with NUMBL regulating notch signaling through degradation of NICD, a modulator of RBPJ. Accordingly, deletion of Rbpj partially corrected osteopetrosis in Tak1-deficient mice. Furthermore, expression of active IKK2 in RBPJ/TAK1-deficient cells significantly restored osteoclastogenesis, indicating that activation of NF-κB is essential for complete rescue of the pathway. Thus, we propose that TAK1 regulates osteoclastogenesis by integrating activation of NF-κB and derepression of NOTCH/RBPJ in myeloid cells through inhibition of NUMBL.
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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.