Ying and Yang of Sphingosine-1-Phosphate Signalling within the Bone

Osteoblast–Osteoclast Communication via S1P. S1P can act directly on osteoblasts via S1PR1/3 receptors to enhance osteoblast maturation and mineralisation []. S1PR1/3 also activates the ERK/p38 signalling pathway to enhance COX2 production [,]. COX2 then elicits the release of RANKL from osteoblasts to enhance osteoclastogenesis via p38-cfos-NFATc1 signalling []. RANK activation of osteoclasts by RANKL also upregulates SPHK1 expression and production, resulting in increased intracellular S1P, which inhibits p38. Inhibition of p38 causes a reduction in osteoclastogenesis, acting as a negative regulator of osteoclast maturation []. S1P released from osteoclasts increases extracellular S1P, which may act as a break on osteoclastogenesis through the S1PR2 receptor on osteoblasts, as S1PR2 acts to enhance the secretion of the RANKL decoy receptor osteoprotegerin (OPG) []. OPG acts to reduce further RANKL-mediated osteoclastogenesis through binding to RANKL. Created in Biorender.com.

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The Ying and Yang of Sphingosine-1-Phosphate Signalling within the Bone. (2023) Kathryn Frost, et al. Int J Mol Sci. 2023 Apr;24(8):6935. Figure: F3. Homo sapiens

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