SPHK1-S1PR1-RANKL Axis Regulates the Interactions Between Macrophages and BMSCs in Inflammatory Bone Loss
| Autor: | Yinghong Zhou, Lingxin Zhu, Willa Shi, Bin Peng, Yin Xiao, Shasha Yang, Lan Xiao, Rong Huang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stromal cell biology Chemistry Endocrinology Diabetes and Metabolism Osteoimmunology Bone resorption Bone remodeling 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Sphingosine kinase 1 RANKL medicine Cancer research biology.protein Orthopedics and Sports Medicine Bone marrow S1PR1 |
| Zdroj: | Journal of Bone and Mineral Research. 33:1090-1104 |
| ISSN: | 0884-0431 |
| DOI: | 10.1002/jbmr.3396 |
| Popis: | Accumulating evidence indicates that the immune and skeletal systems interact with each other through various regulators during the osteoclastogenic process. Among these regulators, the bioactive lipid sphingosine-1-phosphate (S1P), which is synthesized by sphingosine kinase 1/2 (SPHK1/2), has recently been recognized to play a role in immunity and bone remodeling through its receptor sphingosine-1-phosphate receptor 1 (S1PR1). However, little is known regarding the potential role of S1PR1 signaling in inflammatory bone loss. We observed that SPHK1 and S1PR1 were up-regulated in human apical periodontitis, accompanied by macrophage infiltration and enhanced expression of nuclear factor kappa B ligand (RANKL, an indispensable factor in osteoclastogenesis and bone resorption) and increased numbers of S1PR1-RANKL double-positive cells in lesion tissues. Using an in vitro co-culture model of macrophages and bone marrow stromal cells (BMSCs), it was revealed that in the presence of lipopolysaccharide (LPS) stimulation, macrophages could significantly induce SPHK1 activity, which resulted in activated S1PR1 in BMSCs. The activated S1P-S1PR1 signaling was responsible for the increased RANKL production in BMSCs, as S1PR1-blockage abolished this effect. Applying a potent S1P-S1PR1 signaling modulator, Fingolimod (FTY720), in a Wistar rat apical periodontitis model effectively prevented bone lesions in vivo via down-regulation of RANKL production, osteoclastogenesis, and bone resorption. Our data unveiled the regulatory role of SPHK1-S1PR1-RANKL axis in inflammatory bone lesions and proposed a potential therapeutic intervention by targeting this cell-signaling pathway to prevent bone loss. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text