ArticleThe Journal of clinical investigation2000
Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 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.
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.
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Who cites it
275 citing papers in PubMed, 722 citations in OpenAlex.
- Matrix Competence Failure in Osteoporosis: Mechanosensing, Osteoimmune Crosstalk, and Fragility Beyond Bone Mineral Density.Current medical science · 2026Review
- Solasodine, a Natural Steroidal Alkaloid, Attenuates RANKL-Induced Osteoclastogenesis and Bone Resorption: A Study Based on Network Pharmacology and Experimental Validation.Journal of cellular and molecular medicine · 2026Article
- The osteoclast intracellular environment fosters bacterial growth duringbioRxiv : the preprint server for biology · 2026Article
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- Mechanism of ITGB2 in Osteoclast Differentiation in Osteoarthritis.Cell proliferation · 2026Article
- Integrin β3 deficiency unleashes spontaneous pulmonary inflammation by promoting B cell hyperactivation via the CD40-CD40L axis.Frontiers in immunology · 2026Article
- An in vivo assay for osteoclast activity using mouse calvaria.Animal models and experimental medicine · 2026Article
- Ultra-small coordination dihydromyricetin nanodots attenuate alveolar bone resorption in periodontitis through inhibition of ITGB3-Driven osteoclast differentiation.Materials today. Bio · 2025Article
- Moesin controls cell-cell fusion and osteoclast function.The Journal of cell biology · 2025Article
- Formation of Membrane Domains via Actin Waves: A Fundamental Principle in the Generation of Dynamic Structures in Phagocytes.International journal of molecular sciences · 2025Review
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- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Osteoclast-like multinucleated giant cells reinforce polycaprolactone grafts.Frontiers in immunology · 2025Article
- Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration.Advanced therapeutics · 2025Article
- Extracellular derivatives for bone metabolism.Journal of advanced research · 2024Review
- Bone Disease in Primary Hyperparathyroidism-Changes Occurring in Bone Metabolism and New Potential Treatment Strategies.International journal of molecular sciences · 2024Review
- Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis.Science advances · 2024Article
- Beyond resorption: osteoclasts as drivers of bone formation.Cell regeneration (London, England) · 2024Review
- Hem1 is essential for ruffled border formation in osteoclasts and efficient bone resorption.Scientific reports · 2024Article
215 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Osteoclasts express the alphavbeta3 integrin, an adhesion receptor that has been implicated in bone resorption and that is therefore a potential therapeutic target. To assess the role of this heterodimer in skeletal development in vivo, we engineered mice in which the gene for the beta3 integrin subunit was deleted. Bone marrow macrophages derived from these mutants differentiate in vitro into numerous osteoclasts, thus establishing that alphavbeta3 is not necessary for osteoclast recruitment. Furthermore, the closely related integrin, alphavbeta5, does not substitute for alphavbeta3 during cytokine stimulation or authentic osteoclastogenesis. beta3 knockout mice, but not their heterozygous littermates, develop histologically and radiographically evident osteosclerosis with age. Despite their increased bone mass, beta3-null mice contain 3.5-fold more osteoclasts than do heterozygotes. These mutant osteoclasts are, however, dysfunctional, as evidenced by their reduced ability to resorb whale dentin in vitro and the significant hypocalcemia seen in the knockout mice. The resorptive defect in beta3-deficient osteoclasts may reflect absence of matrix-derived intracellular signals, since their cytoskeleton is distinctly abnormal and they fail to spread in vitro, to form actin rings ex vivo, or to form normal ruffled membranes in vivo. Thus, although it is not required for osteoclastogenesis, the integrin alphavbeta3 is essential for normal osteoclast function.
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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.