ArticleThe Journal of cell biology2015
Absence of Dap12 and the αvβ3 integrin causes severe osteopetrosis.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- OSCAR functions as a collagen I receptor to suppress hippo signaling and reprogram lipid metabolism in clear-cell renal cell carcinoma.Cell death & disease · 2026Article
- Topography-based implants for bone regeneration: Design, biological mechanism, and therapeutics.Materials today. Bio · 2025Review
- Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor.Bone research · 2024Article
- Integrins as Drug Targets in Vascular and Related Diseases.International journal of drug discovery and pharmacology · 2024Article
- Role and Regulation of Transcription Factors in Osteoclastogenesis.International journal of molecular sciences · 2023Review
- BAP1 promotes osteoclast function by metabolic reprogramming.Nature communications · 2023Article
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Mechanical regulation of bone remodeling.Bone research · 2022Review
- Nanoporous titanium implant surface promotes osteogenesis by suppressing osteoclastogenesis via integrin β1/FAKpY397/MAPK pathway.Bioactive materials · 2022Article
- Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture.Acta biomaterialia · 2022Article
- Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation.Frontiers in cell and developmental biology · 2022Review
- Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune.Cellular and molecular life sciences : CMLS · 2021Review
- [EJNMMI research · 2021Article
- Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease.Frontiers in cell and developmental biology · 2021Review
- Sorting Nexin 10 as a Key Regulator of Membrane Trafficking in Bone-Resorbing Osteoclasts: Lessons Learned From Osteopetrosis.Frontiers in cell and developmental biology · 2021Article
- Ostm1 from Mouse to Human: Insights into Osteoclast Maturation.International journal of molecular sciences · 2020Review
- Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation.Journal of cellular and molecular medicine · 2020Review
- Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk.Nature communications · 2020Article
- Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations.ACS pharmacology & translational science · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In vitro, ligand occupancy of αvβ3 integrin induces phosphorylation of Dap12, which is essential for osteoclast function. Like mice deleted of only αvβ3, Dap12(-/-) mice exhibited a slight increase in bone mass, but Dap12(-/-) mice, lacking another ITAM protein, FcRγ, were severely osteopetrotic. The mechanism by which FcRγ compensates for Dap12 deficiency is unknown. We find that co-deletion of FcRγ did not exacerbate the skeletal phenotype of β3(-/-) mice. In contrast, β3/Dap12 double-deficient (DAP/β3(-/-)) mice (but not β1/Dap12 double-deficient mice) were profoundly osteopetrotic, reflecting severe osteoclast dysfunction relative to those lacking αvβ3 or Dap12 alone. Activation of OSCAR, the FcRγ co-receptor, rescued Dap12(-/-) but not DAP/β3(-/-)osteoclasts. Thus, the absence of αvβ3 precluded compensation for Dap12 deficiency by FcRγ. In keeping with this, Syk phosphorylation did not occur in OSCAR-activated DAP/β3(-/-) osteoclasts. Thus, FcRγ requires the osteoclast αvβ3 integrin to normalize the Dap12-deficient skeleton.
Indexed as
Identifiers
What OpenQuestion holds
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.