The role of SphK/S1P/S1PR signaling pathway in bone metabolism. 2023

Xuefeng Xu, and Yi Han, and Tianxin Zhu, and Faxin Fan, and Xin Wang, and Yuqing Liu, and Duosheng Luo
Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, China.

There are a large number of people worldwide who suffer from osteoporosis, which imposes a huge economic burden, so it is necessary to explore the underlying mechanisms to achieve better supportive and curative care outcomes. Sphingosine kinase (SphK) is an enzyme that plays a crucial role in the synthesis of sphingosine-1-phosphate (S1P). S1P with paracrine and autocrine activities that act through its cell surface S1P receptors (S1PRs) and intracellular signals. In osteoporosis, S1P is indispensable for both normal and disease conditions. S1P has complicated roles in regulating osteoblast and osteoclast, respectively, and there have been exciting developments in understanding how SphK/S1P/S1PR signaling regulates these processes in response to osteoporosis therapy. Here, we review the proliferation, differentiation, apoptosis, and functions of S1P, specifically detailing the roles of S1P and S1PRs in osteoblasts and osteoclasts. Finally, we focus on the S1P-based therapeutic approaches in bone metabolism, which may provide valuable insights into potential therapeutic strategies for osteoporosis.

UI MeSH Term Description Entries
D010024 Osteoporosis Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis. Age-Related Osteoporosis,Bone Loss, Age-Related,Osteoporosis, Age-Related,Osteoporosis, Post-Traumatic,Osteoporosis, Senile,Senile Osteoporosis,Osteoporosis, Involutional,Age Related Osteoporosis,Age-Related Bone Loss,Age-Related Bone Losses,Age-Related Osteoporoses,Bone Loss, Age Related,Bone Losses, Age-Related,Osteoporoses,Osteoporoses, Age-Related,Osteoporoses, Senile,Osteoporosis, Age Related,Osteoporosis, Post Traumatic,Post-Traumatic Osteoporoses,Post-Traumatic Osteoporosis,Senile Osteoporoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000081025 Sphingosine-1-Phosphate Receptors A subfamily of lysophospholipid receptors with specificity for sphingosine-1-phosphate (e.g., FINGOLIMOD), sphinganine 1-phosphate, 4-hydroxysphinganine 1-phosphate. Sphingosine-1-Phosphate Receptor 1,Sphingosine-1-Phosphate Receptor 2,Sphingosine-1-Phosphate Receptor 3,Sphingosine-1-Phosphate Receptor 4,Sphingosine-1-Phosphate Receptor 5,AGR16 Protein,EDG5 Protein,Edg Receptors,Edg-5 Receptor,G-Protein Coupled Receptor H218,H218 Protein,Nrg-1 Receptor,Receptor, Sphingosine-1-Phosphate,S1P Receptor,S1P1 Receptor,S1P2 Receptor,S1P3 Receptor,S1P4 Receptor,S1P5 Receptor,Sphingosine 1-Phosphate Receptor,Sphingosine-1-Phosphate Receptor,Edg 5 Receptor,G Protein Coupled Receptor H218,Nrg 1 Receptor,Sphingosine 1 Phosphate Receptor,Sphingosine 1 Phosphate Receptor 1,Sphingosine 1 Phosphate Receptor 2,Sphingosine 1 Phosphate Receptor 3,Sphingosine 1 Phosphate Receptor 4,Sphingosine 1 Phosphate Receptor 5,Sphingosine 1 Phosphate Receptors
D013110 Sphingosine An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed) 4-Sphingenine,4 Sphingenine
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D049349 Receptors, Lysosphingolipid A subfamily of lysophospholipid receptors with specificity for LYSOSPHINGOLIPIDS such as sphingosine-1-phosphate and sphingosine phosphorylcholine. Lysosphingolipid Receptors,Lysosphingolipid Receptor,Receptor, Lysosphingolipid

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