ArticleEuropean journal of clinical investigation2012
Phospholipase Cγ2 is required for basal but not oestrogen deficiency-induced bone resorption.
Article in European journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- 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
- Review
- Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models.The Journal of experimental medicine · 2023Article
- Fluorescence-Based Real-Time Analysis of Osteoclast Development.Frontiers in cell and developmental biology · 2021Article
- Phosphoinositide-specific phospholipase C isoforms are conveyed by osteosarcoma-derived extracellular vesicles.Journal of cell communication and signaling · 2020Article
- Dysbacteriosis-Derived Lipopolysaccharide Causes Embryonic Osteopenia through Retinoic-Acid-Regulated DLX5 Expression.International journal of molecular sciences · 2020Article
- Osteoclast Signal Transduction During Bone Metastasis Formation.Frontiers in cell and developmental biology · 2020Review
- The roles of Orai and Stim in bone health and disease.Cell calcium · 2019Review
- Significance of the Tks4 scaffold protein in bone tissue homeostasis.Scientific reports · 2019Article
- Hematopoietic or Osteoclast-Specific Deletion of Syk Leads to Increased Bone Mass in Experimental Mice.Frontiers in immunology · 2019Article
- Role of the Btk-PLCMediators of inflammation · 2019Article
- Different Calcium and Src Family Kinase Signaling in Mac-1 Dependent Phagocytosis and Extracellular Vesicle Generation.Frontiers in immunology · 2019Article
- The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita.The Journal of investigative dermatology · 2017Article
- Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo.Nature communications · 2016Article
- U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C.SpringerPlus · 2016Article
- Stauntonia hexaphylla (Lardizabalaceae) leaf methanol extract inhibits osteoclastogenesis and bone resorption activity via proteasome-mediated degradation of c-Fos protein and suppression of NFATc1 expression.BMC complementary and alternative medicine · 2015Article
- The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment.The Journal of experimental medicine · 2014Article
- Ezrin silencing remodulates the expression of Phosphoinositide-specific Phospholipase C enzymes in human osteosarcoma cell lines.Journal of cell communication and signaling · 2014Article
- The phosphoinositide 3-kinase isoform PI3Kβ regulates osteoclast-mediated bone resorption in humans and mice.Arthritis & rheumatology (Hoboken, N.J.) · 2014Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundOsteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2-deficient (PLCγ2(-/-) ) mice. MATERIALS AND
methodsThe trabecular architecture of long bone metaphyses was tested by micro-CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLCγ2 phosphorylation were tested on in vitro osteoclast and macrophage cultures.
resultsPLCγ2(-/-) mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLCγ2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLCγ2 was phosphorylated in a Src-family-dependent manner upon macrophage adhesion but not upon stimulation by M-CSF or RANKL. Surprisingly, ovariectomy-induced bone resorption in PLCγ2(-/-) mice was similar to, or even more robust than, that in wild-type animals.
conclusionsOur results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiency-induced bone resorption utilizes different signalling pathways and that PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis.
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