sphingosine-1-phosphate and Periodontitis

The fundamental interaction between the immune and skeletal systems, termed as osteoimmunology, has been demonstrated to play indispensable roles in the maintenance of balance between bone resorption and formation. The pleiotropic sphingolipid metabolite, sphingosine 1-phosphate (S1P), together with its cognate receptor, sphingosine-1-phosphate receptor-1 (S1PR1), are known as key players in osteoimmunology due to the regulation on both immune system and bone remodeling. The role of S1P-S1PR1 signaling in bone remodeling can be directly targeting both osteoclastogenesis and osteogenesis. Meanwhile, inflammatory cell function and polarization in both adaptive immune (T cell subsets) and innate immune cells (macrophages) are also regulated by this signaling axis, suggesting that S1P-S1PR1 signaling could aslo indirectly regulate bone remodeling

Topics: Animals; Arthritis, Rheumatoid; Bone Remodeling; Bone Resorption; Humans; Lysophospholipids; Macrophages; Periodontitis; Signal Transduction; Sphingosine; Sphingosine-1-Phosphate Receptors; Spondylarthritis; T-Lymphocytes

Sphingosine-1-phosphate (S1P) is a pleiotropic sphingophospholipid generated from the phosphorylation of sphingosine by sphingosine kinases (SPHKs). S1P has been experimentally demonstrated to modulate an array of cellular processes such as cell proliferation, cell survival, cell invasion, vascular maturation, and angiogenesis by binding with any of the five known G-protein-coupled sphingosine 1 phosphate receptors (S1P1-5) on the cell surface in an autocrine as well as a paracrine manner. Recent studies have shown that the S1P receptors (S1PRs) and SPHKs are the key targets for modulating the pathophysiological consequences of various debilitating diseases, such as cancer, sepsis, rheumatoid arthritis, ulcerative colitis, and other related illnesses. In this article, we recapitulate these novel discoveries relative to the S1P/S1PR axis, necessary for the proper maintenance of health, as well as the induction of tumorigenic, angiogenic, and inflammatory stimuli that are vital for the development of various diseases, and the novel therapeutic tools to modulate these responses in oral biology and medicine.

Topics: Animals; Atherosclerosis; Autoimmune Diseases; Cell Proliferation; Gene Expression Regulation, Enzymologic; GTP-Binding Protein alpha Subunits; GTP-Binding Protein Regulators; Humans; Lymphatic Metastasis; Lysophospholipids; Mandibular Condyle; Neovascularization, Pathologic; Neurogenic Inflammation; Periodontitis; Phosphotransferases (Alcohol Group Acceptor); Receptors, Lysosphingolipid; Signal Transduction; Sphingosine

To explore the potential mechanisms of neuroinflammation (microglia, blood-brain barrier [BBB] permeability, and the sphingosine-1-phosphate [S1P] pathways) resulting from the association between periodontitis and depression in rats.. This pre-clinical in vivo experimental study used Wistar rats, in which experimental periodontitis (P) was induced by using oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum. Then, a chronic mild stress (CMS) model was implemented to induce a depressive-like behaviour, resulting in four groups: P with CMS (P+CMS+), P without CMS (P+CMS-), CMS without P (P-CMS+), and control (P-CMS-). After harvesting brain samples, protein/mRNA expression analyses and fluorescence immunohistochemistry were performed in the frontal cortex (FC). Results were analysed by ANOVA.. CMS exposure increased the number of microglia (an indicator of neuroinflammation) in the FC. In the combined model (P+CMS+), there was a decrease in the expression of tight junction proteins (zonula occludens-1 [ZO-1], occludin) and an increase in intercellular and vascular cell adhesion molecules (ICAM-1, VCAM-1) and matrix metalloproteinase 9 (MMP9), suggesting a more severe disruption of the BBB. The enzymes and receptors of S1P were also differentially regulated.. Microglia, BBB permeability, and S1P pathways could be relevant mechanisms explaining the association between periodontitis and depression.

Topics: Animals; Blood-Brain Barrier; Depression; Neuroinflammatory Diseases; Periodontitis; Rats; Rats, Wistar

This study evaluated changes in the levels of Sphingosine-1-Phosphate (S1P) and Sphingosine Kinase (SPHK) activity in response to non-surgical periodontal treatment in humans.. Diseased (n = 65) and healthy sites (n = 72) were screened in 18 patients with localized periodontitis stage II or III. Periodontal clinical parameters were recorded, and the gingival crevicular fluid (GCF) collected at baseline, 30 and 90 days of non-surgical treatment. Internal control sites without attachment loss/bleeding were sampled at baseline and after 90 days of treatment. SPHK activity and S1P levels and SPHK 1/2 isoforms were determined in the GCF at different time points using ELISA.. Non-surgical treatment caused significant improvement in all periodontal clinical parameters (p < 0.01). Activity of SPHK and S1P levels was decreased (p < 0.05) 30 days after treatment and continued up to 90 days (p < 0.01); control sites remained unchanged throughout the study and resembled treated sites at 3 months (p > 0.05). SPHK1 levels presented decrease after periodontal treatment (p < 0.001). SPHK2 levels were lower than SPHK1 (p < 0.001) and remained unchanged.. S1P levels and SPHK activity decreased within 3 months of non-surgical periodontal treatment, which were correlated with improvements in periodontal parameters. Only SPHK1 levels varied significantly in the states of health and disease.

Topics: Humans; Lysophospholipids; Periodontitis; Periodontium; Phosphotransferases (Alcohol Group Acceptor)