ArticleArthritis & rheumatology (Hoboken, N.J.)2014
The phosphoinositide 3-kinase isoform PI3Kβ regulates osteoclast-mediated bone resorption in humans and mice.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Extracellular vesicle-mediated crosstalk in bone: miR-150-5p as a mechanosensitive regulator of osteoclastogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Research on Bone Cells in Health and Disease.International journal of molecular sciences · 2024Article
- De novo steroidogenesis in tumor cells drives bone metastasis and osteoclastogenesis.Cell reports · 2024Article
- BAP1 promotes osteoclast function by metabolic reprogramming.Nature communications · 2023Article
- Cholesterol inhibits autophagy in RANKL-induced osteoclast differentiation through activating the PI3K/AKT/mTOR signaling pathway.Molecular biology reports · 2022Article
- MicroRNA-loaded biomaterials for osteogenesis.Frontiers in bioengineering and biotechnology · 2022Review
- Fluorescence-Based Real-Time Analysis of Osteoclast Development.Frontiers in cell and developmental biology · 2021Article
- Article
- Osteoclast Signal Transduction During Bone Metastasis Formation.Frontiers in cell and developmental biology · 2020Review
- TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- PI3K activation increases SDF-1 production and number of osteoclast precursors, and enhances SDF-1-mediated osteoclast precursor migration.Bone reports · 2019Article
- PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling.Endocrinology · 2019Review
- Gene Expression Profiles of Peripheral Blood Monocytes in Osteoarthritis and Analysis of Differentially Expressed Genes.BioMed research international · 2019Article
- Hematopoietic or Osteoclast-Specific Deletion of Syk Leads to Increased Bone Mass in Experimental Mice.Frontiers in immunology · 2019Article
- Compensation between CSF1R+ macrophages and Foxp3+ Treg cells drives resistance to tumor immunotherapy.JCI insight · 2018Article
- Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies.Cellular and molecular life sciences : CMLS · 2017Article
- Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells.Science signaling · 2016Article
- Editorial: lipid kinases and bone homeostasis: lessons learned from phosphoinositide 3-kinase isoform-specific knockouts.Arthritis & rheumatology (Hoboken, N.J.) · 2014Article
- PI-3 kinase p110β: a therapeutic target in advanced prostate cancers.American journal of clinical and experimental urology · 2014Review
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
objectiveWhile phosphoinositide 3-kinases (PI3Ks) are involved in various intracellular signal transduction processes, the specific functions of the different PI3K isoforms are poorly understood. We have previously shown that the PI3Kβ isoform is required for arthritis development in the K/BxN serum-transfer model. Since osteoclasts play a critical role in pathologic bone loss during inflammatory arthritis and other diseases, we undertook this study to test the role of PI3Kβ in osteoclast development and function using a combined genetic and pharmacologic approach.
methodsThe role of PI3Kβ in primary human and murine osteoclast cultures was tested with the PI3Kβ-selective inhibitor TGX221 and by using PI3Kβ(-/-) mice. The trabecular bone architecture of PI3Kβ(-/-) mice was evaluated using micro-computed tomography and histomorphometric analyses.
resultsThe expression of PI3Kβ was strongly and specifically up-regulated during in vitro osteoclast differentiation. In vitro development of large multinucleated osteoclasts from human or murine progenitors and their resorption capacity were strongly reduced by the PI3Kβ inhibitor TGX221 or by the genetic deficiency of PI3Kβ. This was likely due to defective cytoskeletal reorganization and vesicular trafficking, since PI3Kβ(-/-) mouse multinucleated cells failed to form actin rings and retained intracellular acidic vesicles and cathepsin K. In contrast, osteoclast-specific gene expression and the survival and apoptosis of osteoclasts were not affected. PI3Kβ(-/-) mice had significantly increased trabecular bone volume and showed abnormal osteoclast morphology with defective resorption pit formation.
conclusionPI3Kβ plays an important role in osteoclast development and function and is required for in vivo bone homeostasis.
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