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

Lincheng Zhang,Yiran Wang,Yutong Dong,Yueqi Chen,Shiwu Dong,Wenhui Hu

doi:10.1111/jcmm.15155

Lincheng Zhang, Yiran Wang + Show 4 more

Open Access

https://doi.org/10.1111/jcmm.15155

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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.

Highlights

Bone is regarded as a highly dynamic tissue that constantly undergoes cycles of bone resorption and bone formation
The whole cycle is divided into three phases: (a) the interaction of osteoclast precursors (OCPs) and osteoblasts (OBs) on the bone surface, including OCP recruitment, RANKL-RANK binding and adhesion to the bone surface; (b) the differentiation of osteoblast precursors (OBPs) is facilitated by various cytokines from mature osteoclasts; and (c) the apoptosis of osteoclasts (OCs), as well as mineralization of the bone matrix.[1]
During these OCPs and OBPs migrate to the bone surface, and various coupling factors, such as receptor activator of nuclear factor-κ B ligand (RANKL), have a dramatic influence on the bone regeneration cycle