ArticleLipids in health and disease2015
FTY720 inhibited proinflammatory cytokine release and osteoclastogenesis induced by Aggregatibacter actinomycetemcomitans.
Article in Lipids in health and disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Association between Serum Uric Acid Levels and Salivary Microbiota in Patients with Obstructive Sleep Apnea.Journal of microbiology and biotechnology · 2025Article
- Orientin: a comprehensive review of a promising bioactive flavonoid.Inflammopharmacology · 2025Review
- Potential of Liposomal FTY720 for Bone Regeneration: Proliferative, Osteoinductive, Chemoattractive, and Angiogenic Properties Compared to Free Bioactive Lipid.International journal of nanomedicine · 2025Article
- Orientin suppresses osteoclastogenesis and ameliorates ovariectomy-induced osteoporosis via suppressing ROS production.Food science & nutrition · 2023Article
- FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-Journal of immunology research · 2023Article
- Network Pharmacological Study on Mechanism of the Therapeutic Effect of Modified Duhuo Jisheng Decoction in Osteoporosis.Frontiers in endocrinology · 2022Article
- Fingolimod Nanoemulsions at Different Particle Sizes Define the Fate of Spinal Cord Injury Recovery.BioMed research international · 2022Article
- Exosomal miR-19a and IBSP cooperate to induce osteolytic bone metastasis of estrogen receptor-positive breast cancer.Nature communications · 2021Article
- Targeting S1PRs as a Therapeutic Strategy for Inflammatory Bone Loss Diseases-Beyond Regulating S1P Signaling.International journal of molecular sciences · 2021Review
- Increased Sphingosine-1-Phosphate Serum Concentrations in Subjects with Periodontitis: A Matter of Inflammation.Journal of inflammation research · 2021Article
- SIV-Mediated Synaptic Dysfunction Is Associated with an Increase in Synapsin Site 1 Phosphorylation and Impaired PP2A Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- SPHK-2 Promotes the Particle-Induced Inflammation of RAW264.7 by Maintaining Consistent Expression of TNF-α and IL-6.Inflammation · 2018Article
- Rapamycin and FTY720 Alleviate Atherosclerosis by Cross Talk of Macrophage Polarization and Autophagy.BioMed research international · 2018Article
- Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.Pharmacological research · 2017Review
- Administration of FTY720 during Tourniquet-Induced Limb Ischemia Reperfusion Injury Attenuates Systemic Inflammation.Mediators of inflammation · 2017Article
- Sphingosine-1-Phosphate Receptor 2 Regulates Proinflammatory Cytokine Production and Osteoclastogenesis.PloS one · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPeriodontitis is a bacteria-driven inflammatory bone loss disease. Previous studies showed that the oral pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) stimulated the generation of sphingosine 1 phosphate (S1P). In addition, S1P signaling regulated the migration of osteoclast precursors and affected osteoclastogenesis. Furthermore, treatment with FTY720 (also called fingolimod, a modulator of multiple S1P receptors) alleviated osteoporosis and suppressed arthritis in animals. This study determined the effect of FTY720 on proinflammatory cytokine production and osteoclastogenesis in murine bone marrow cells with or without A. actinomycetemcomitans stimulation.
methodsMurine bone marrow-derived monocytes and macrophages (BMMs) were treated with vehicle ethanol or FTY720, and were either unstimulated or stimulated for 0.5 to 6 h with A. actinomycetemcomitans. The protein levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the media of BMMs were quantified by enzyme-linked immunosorbent assay (ELISA). Protein expressions, including phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, p-extracellular signal-regulated kinase (p-ERK), PI3K, Akt, and ERK were evaluated by Western blot. In addition, murine bone marrow-derived pre-osteoclasts were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) for three days. Then the cells were treated with either vehicle or FTY720 and were either unstimulated or stimulated with A. actinomycetemcomitans for 4 to 24 h. Control cells were treated with M-CSF alone with or without bacterial stimulation. Osteoclasts were stained by tartrate-resistant acid phosphatase (TRAP) staining. The mRNA levels of osteoclastogenic factors, including nuclear factor of activated T-cells cytoplasmic calcineurin-dependent 1 (Nfatc1), cathepsin K (Ctsk), acid phosphatase 5 (Acp5), osteoclast-associated receptor (Oscar), and RANKL were quantified by quantitative real-time polymerase chain reaction (PCR).
resultsFTY720 dose-dependently inhibited IL-1β, IL-6, and TNF-α protein levels induced by A. actinomycetemcomitans in BMMs compared with controls. Additionally, FTY720 attenuated p-PI3K, p-Akt, and p-ERK expressions induced by A. actinomycetemcomitans. Furthermore, FTY720 suppressed osteoclastogenesis in bone marrow-derived pre-osteoclasts with or without bacterial stimulation and reduced the mRNA levels of Nfatc1, Ctsk, Acp5, and Oscar, but not RANKL in bone marrow-derived pre-osteoclasts.
conclusionFTY720 inhibited proinflammatory cytokine production and suppressed osteoclastogenesis, supporting FTY720 as a potential therapy for inflammatory bone loss diseases.
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