ArticleThe Journal of endocrinology2019
Homer2 and Homer3 modulate RANKL-induced NFATc1 signaling in osteoclastogenesis and bone metabolism.
Article in The Journal of endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- DMOG pretreatment restores osteogenic-adipogenic balance and mitochondrial function in ONFH BMSCs through the HIF-1α/Homer3 pathway.Stem cell research & therapy · 2026Article
- A Novel Frameshift Variant c.1023_1029del (p.Asp342ArgfsTer54) Leading to Extended Incorrect Protein C Termini in HOMER2 Causing Autosomal Dominant Nonsyndromic Hearing Loss.Journal of clinical laboratory analysis · 2026Article
- HOMER3 and its correlation with immune-infiltrating M2 macrophages in colorectal cancer.Discover oncology · 2025Article
- ELK4 induced upregulation of HOMER3 promotes the proliferation and metastasis in glioma via Wnt/β-catenin/EMT signaling pathway.Biology direct · 2025Article
- Bioinformatics screening and clinical validation of CircRNA and related miRNA in male osteoporosis.BMC musculoskeletal disorders · 2025Article
- The Effect of Grape Seed Extract on the Alveolar, Jaw, and Skeletal Bone Remodeling: A Scoping Review.European journal of dentistry · 2024Article
- Novel Heredity Basis of the Four-Horn Phenotype in Sheep Using Genome-Wide Sequence Data.Animals : an open access journal from MDPI · 2023Article
- Integrative analysis reveals a lineage-specific circular RNA landscape for adipo-osteogenesis of human mesenchymal stem cells.Stem cell research & therapy · 2022Article
- Influence of atherosclerosis on the molecular expression of the TRPC1/BK signal complex in the aortic smooth muscles of mice.Experimental and therapeutic medicine · 2022Article
- Article
- Assessment of Heterozygosity and Genome-Wide Analysis of Heterozygosity Regions in Two Duroc Pig Populations.Frontiers in genetics · 2021Article
- Sestrin2 Regulates Osteoclastogenesis via the p62-TRAF6 Interaction.Frontiers in cell and developmental biology · 2021Article
- Effect of combined application of iguratimod in the treatment of active rheumatoid arthritis on bone metabolism, Th17 cells and Treg cells.American journal of translational research · 2021Article
- The Role of CaInternational journal of molecular sciences · 2020Review
- Distinct and Overlapping Expression Patterns of the Homer Family of Scaffolding Proteins and Their Encoding Genes in Developing Murine Cephalic Tissues.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The receptor activator of nuclear factor-kappa B ligand (RANKL) induces osteoclastogenesis by induction of Ca2+ oscillation, calcineurin activation and translocation into the nucleus of nuclear factor of activated T cells type c1 (NFATc1). Homer proteins are scaffold proteins. They regulate Ca2+ signaling by modulating the activity of multiple Ca2+ signaling proteins. Homers 2 and 3, but not Homer1, also independently affect the interaction between NFATc1 and calcineurin. However, to date, whether and how the Homers are involved in osteoclastogenesis remains unknown. In the present study, we investigated Homer2 and Homer3 roles in Ca2+ signaling and NFATc1 function during osteoclast differentiation. Deletion of Homer2/Homer3 (Homer2/3) markedly decreased the bone density of the tibia, resulting in bone erosion. RANKL-induced osteoclast differentiation is greatly facilitated in Homer2/3 DKO bone marrow-derived monocytes/macrophages (BMMs) due to increased NFATc1 expression and nuclear translocation. However, these findings did not alter RANKL-induced Ca2+ oscillations. Of note, RANKL treatment inhibited Homer proteins interaction with NFATc1, but it was restored by cyclosporine A treatment to inhibit calcineurin. Finally, RANKL treatment of Homer2/3 DKO BMMs significantly increased the formation of multinucleated cells. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation. Specifically, we found that Homer2 and Homer3 regulate NFATc1 function through its interaction with calcineurin to regulate RANKL-induced osteoclastogenesis and bone metabolism.
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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.