ArticleJournal of immunology (Baltimore, Md. : 1950)2009
IL-10 suppresses calcium-mediated costimulation of receptor activator NF-kappa B signaling during human osteoclast differentiation by inhibiting TREM-2 expression.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 120 citations in OpenAlex.
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- 6-Hydroxyflavone Attenuates Inflammatory Osteolysis by Inhibiting Osteoclast Activation via the Nrf2 and Calcium Signaling Pathways.Inflammation · 2026Article
- Role of Cytokines in Bone Diseases and Their Therapeutic Application.ImmunoTargets and therapy · 2026Review
- Effects ofJournal of Taibah University Medical Sciences · 2025Article
- Chronic stress and the IL-10-mediated immunoregulatory loop in the pathogenesis of periodontitis.Clinical science (London, England : 1979) · 2025Review
- HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma.Neuroscience bulletin · 2025Article
- Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis.Frontiers in cell and developmental biology · 2025Review
- Identification of lactylation-related biomarkers in osteoporosis from transcriptome and single-cell data.Frontiers in endocrinology · 2025Article
- Gingival fibroblasts produce paracrine signals that affect osteoclastogenesis in vitro.Bone reports · 2024Article
- SREBP2 restricts osteoclast differentiation and activity by regulating IRF7 and limits inflammatory bone erosion.Bone research · 2024Article
- Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.International journal of molecular sciences · 2024Review
- IKK/NF-κB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS-induced inflammatory osteolysis.Cell proliferation · 2024Article
- Comparative Study of the Cytokine Profiles of Serum and Tissues from Patients with the Ossification of the Posterior Longitudinal Ligament.Biomedicines · 2023Article
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- The effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis: a review.Frontiers in immunology · 2023Review
- Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives.International journal of molecular sciences · 2022Review
- Revealing Potential Spinal Cord Injury Biomarkers and Immune Cell Infiltration Characteristics in Mice.Frontiers in genetics · 2022Article
- Review
- Role of nitric oxide in orthodontic tooth movement (Review).International journal of molecular medicine · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Induction of effective osteoclastogenesis by RANK (receptor activator of NF-kappaB) requires costimulation by ITAM-coupled receptors. In humans, the TREM-2 (triggering receptor expressed on myeloid cells 2) ITAM-coupled receptor plays a key role in bone remodeling, as patients with TREM-2 mutations exhibit defective osteoclastogenesis and bone lesions. We have identified a new rapidly induced costimulatory pathway for RANK signaling that is dependent on TREM-2 and mediated by calcium signaling. TREM-2-dependent calcium signals are required for RANK-mediated activation of calcium/calmodulin-dependent protein kinase (CaMK)II and downstream MEK and ERK MAPKs that are important for osteoclastogenesis. IL-10 inhibited RANK-induced osteoclastogenesis and selectively inhibited calcium signaling downstream of RANK by inhibiting transcription of TREM-2. Down-regulation of TREM-2 expression resulted in diminished RANKL-induced activation of the CaMK-MEK-ERK pathway and decreased expression of the master regulator of osteoclastogenesis NFATc1. These findings provide a new mechanism of inhibition of human osteoclast differentiation. The results also yield insights into crosstalk between ITAM-coupled receptors and heterologous receptors such as RANK, and they identify a mechanism by which IL-10 can suppress cellular responses to TNFR family members.
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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.