Effect of Sphingosine-1-phosphate on Osteoclast Formation

Abstract

Sphingosine-1-phosphate (S1P), which is mainly erythrocyte-derived, is a lipid mediator, which exists at high levels in plasma and acts on its receptors. S1P displays physiological functions, e.g., cell proliferation, cell migration and alteration of cellular morphology, through the S1P receptor. Among S1P receptors, stimulus via S1P_1/3 accelerates cell movement; in contrast, activation of S1P₂ inhibits cell movement. Osteoclasts are bone resorption cells that are fused and multinucleated through osteoclast precursor cells derived from hematopoietic stem cells. However, whether proliferation and fusion of osteoclast precursor cells are controlled and adjusted by the lipid mediator is unknown. This study examined the influence of S1P in terms of control of osteoclastic differentiation employing the osteoclastic cell formation process. Upon separation of erythrocytes from all bone marrow cells, the level of osteoclast formation decreased; subsequently, following the addition of S1P, the number of cells recovered. Furthermore, the number of osteoclasts decreased in the S1P_1/3 antagonist. RT-PCR revealed that S1P₁ mRNA expression is higher in bone marrow cells in comparison to osteoclasts; in contrast, S1P₂ mRNA expression is higher in osteoclastic cells. Therefore, red blood cells are involved in the process of osteoclast formation as the S1P source in plasma and proliferation of osteoclastic cells are controlled via inhibition of S1P_1/3. On the other hand, S1P₁ function was aided and cell differentiation was accelerated by inhibition of S1P₂. Based on the aforementioned findings, it is clear that S1P plays an important role in the regulation of osteoclast differentiation.