Sphingosine-1-phosphate (S1P) receptors: Promising drug targets for treating bone-related diseases

J Cell Mol Med. 2020 Apr;24(8):4389-4401. doi: 10.1111/jcmm.15155. Epub 2020 Mar 10.

Abstract

Sphingosine-1-phosphate (S1P) is a natural bioactive lipid molecule and a common first or second messenger in the cardiovascular and immune systems. By binding with its receptors, S1P can serve as mediator of signalling during cell migration, differentiation, proliferation and apoptosis. Although the predominant role of S1P in bone regeneration has been noted in many studies, this role is not as well-known as its roles in the cardiovascular and immune systems. In this review, we summarize previous research on the role of S1P receptors (S1PRs) in osteoblasts and osteoclasts. In addition, S1P is regarded as a bridge between bone resorption and formation, which brings hope to patients with bone-related diseases. Finally, we discuss S1P and its receptors as therapeutic targets for treating osteoporosis, inflammatory osteolysis and bone metastasis based on the biological effects of S1P in osteoclastic/osteoblastic cells, immune cells and tumour cells.

Keywords: S1P receptors; cancer-related bone metastasis; inflammatory osteolysis; osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Bone Resorption / genetics*
  • Bone Resorption / pathology
  • Humans
  • Lysophospholipids / genetics*
  • Neoplasm Metastasis
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteolysis / genetics
  • Osteolysis / pathology
  • Osteoporosis / genetics
  • Osteoporosis / pathology
  • Sphingosine / analogs & derivatives*
  • Sphingosine / genetics
  • Sphingosine-1-Phosphate Receptors / genetics*
  • Sphingosine-1-Phosphate Receptors / metabolism

Substances

  • Lysophospholipids
  • Sphingosine-1-Phosphate Receptors
  • sphingosine 1-phosphate
  • Sphingosine