ArticleCell death & disease2019
TRAIL inhibits RANK signaling and suppresses osteoclast activation via inhibiting lipid raft assembly and TRAF6 recruitment.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Thioredoxin-2 Alleviates Osteoporosis by Restraining FOXO3a Nuclear Translocation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Role of TRAIL in mediating the effect of lipidome on breast cancer: a Mendelian randomization study.Translational cancer research · 2026Article
- New Glass-Ceramics in the System CaMaterials (Basel, Switzerland) · 2025Article
- Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization.Cell genomics · 2025Article
- The potential link between the development of Alzheimer's disease and osteoporosis.Biogerontology · 2025Review
- Stephanine Protects Against Osteoporosis by Suppressing Osteoclastogenesis via Inhibition of the RANKL-RANK Interaction.Journal of cellular and molecular medicine · 2024Article
- Acute hyperlipidemia has transient effects on large-scale bone regeneration in male mice.Scientific reports · 2024Article
- Systemic Inflammatory Regulators Associated with Osteoporosis: A Bidirectional Mendelian Randomization Study.Calcified tissue international · 2024Article
- Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets.Molecular medicine (Cambridge, Mass.) · 2024Review
- Structure and function of the membrane microdomains in osteoclasts.Bone research · 2023Review
- Article
- USP1 Inhibits NF-κB/NLRP3 Induced Pyroptosis through TRAF6 in Osteoblastic MC3T3-E1 Cells.Journal of musculoskeletal & neuronal interactions · 2022Article
- Osteoporosis pathogenesis and treatment: existing and emerging avenues.Cellular & molecular biology letters · 2022Review
- Natural Killer Cells Infiltration in the Joints Exacerbates Collagen-Induced Arthritis.Frontiers in immunology · 2022Article
- 6-Shogaol promotes bone resorption and accelerates orthodontic tooth movement through the JNK-NFATc1 signaling axis.Journal of bone and mineral metabolism · 2021Article
- Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point.Cells · 2021Review
- Gamabufotalin Inhibits Osteoclastgenesis and Counteracts Estrogen-Deficient Bone Loss in Mice by Suppressing RANKL-Induced NF-κB and ERK/MAPK Pathways.Frontiers in pharmacology · 2021Article
- Article
- Corilagin suppresses RANKL-induced osteoclastogenesis and inhibits oestrogen deficiency-induced bone loss via the NF-κB and PI3K/AKT signalling pathways.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human osteoclast formation from mononuclear phagocyte precursors involves interactions between members of the tumor necrosis factor (TNF) ligand superfamily and their receptors. Recent evidence indicated that TNF-α-related apoptosis-inducing ligand (TRAIL) induces osteoclast differentiation via a TRAF6-dependent signaling pathway; but paradoxically, it inhibits RANK ligand (RANKL)-induced osteoclast differentiation. Although a number of signaling pathways were linked to the RANK and osteoclastogenesis, it is not known how TRAIL regulates RANK signaling. In this study, we demonstrate that TRAIL regulates RANK-induced osteoclastogenesis in terms of the assembly of lipid raft-associated signaling complexes. RANKL stimulation induced recruitment of TRAF6, c-Src, and DAP-12 into lipid rafts. However, the RANKL-induced assembly of lipid raft-associated signaling complexes and TRAF6 recruitment was abolished in the presence of TRAIL. TRAIL-induced dissociation of RANKL-induced lipid raft signaling complexes was reversed by treatment with TRAIL receptor (TRAIL-R) siRNA or an anti-TRAIL-R blocking antibody, indicating that TRAIL mediates suppression of RANKL-induced lipid raft signaling via interactions with TRAIL-R. Finally, we demonstrated that TRAIL suppressed inflammation-induced bone resorption and osteoclastogenesis in a collagen-induced arthritis (CIA) rat animal model. Our results provide a novel apoptosis-independent role of TRAIL in regulating RANK signaling and suppresses osteoclast activation via inhibiting lipid raft assembly and TRAF6 recruitment.
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