Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling

Jiyoon Ryu, Hyung Joon Kim, Eun Ju Chang, Hao Huang, Yoshiko Banno, Hong Hee Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

247 Scopus citations


Sphingosine 1-phosphate (S1P), produced by sphingosine kinase (SPHK), acts both by intracellular and extracellular modes. We evaluated the role of SPHK1 and S1P in osteoclastogenesis using bone marrow-derived macrophage (BMM) single and BMM/osteoblast coculture systems. In BMM single cultures, the osteoclastogenic factor receptor activator of NF-κB ligand (RANKL) upregulated SPHK1 and increased S1P production and secretion. SPHK1 siRNA enhanced and SPHK1 overexpression attenuated osteoclastogenesis via modulation of p38 and ERK activities, and NFATc1 and c-Fos levels. Extracellular S1P had no effect in these cultures. These data suggest that intracellular S1P produced in response to RANKL forms a negative feedback loop in BMM single cultures. In contrast, S1P addition to BMM/osteoblast cocultures greatly increased osteoclastogenesis by increasing RANKL in osteoblasts via cyclooxygenase-2 and PGE2 regulation. S1P also stimulated osteoblast migration and survival. The RANKL elevation and chemotactic effects were also observed with T cells. These results indicate that secreted S1P attracts and acts on osteoblasts and T cells to augment osteoclastogenesis. Taken together, S1P plays an important role in osteoclastogenesis regulation and in communication between osteoclasts and osteoblasts or T cells.

Original languageEnglish (US)
Pages (from-to)5840-5851
Number of pages12
JournalEMBO Journal
Issue number24
StatePublished - Dec 13 2006


  • Osteoclast differentiation
  • Osteoclast-osteoblast coupling
  • Sphingosine 1-phosphate
  • Sphingosine kinase

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Molecular Biology
  • General Neuroscience


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