title: Psychosine inhibits osteoclastogenesis and bone resorption via G protein-coupled receptor 65.
abstract: BACKGROUND
  It was recently reported that G protein-coupled receptor 65 (GPR65) suppresses ovariectomy-induced bone loss.
  
  
  OBJECTIVE
  The present study investigated the role of the lysosphingolipid psychosine, a GPR65 ligand, on osteoclastic differentiation and bone resorption.
  
  
  METHODS
  Osteoclasts were differentiated from mouse bone marrow macrophages. Tartrate-resistant acid phosphatase-positive multinucleated cells were considered to be osteoclasts, and the resorption area was measured by incubating the cells on dentine discs. The expression levels of osteoclast differentiation markers were assessed by qRT-PCR. GPR65 siRNA and its scrambled siRNA were transfected with lipofectamine. Intracellular cyclic adenosine monophosphate (cAMP) levels were assessed using a direct enzyme immunoassay.
  
  
  RESULTS
  Psychosine inhibited osteoclastogenesis and in vitro bone resorption without any significant effect on the viability of pre-osteoclasts, decreased the expression of osteoclast differentiation markers significantly, and increased intracellular cAMP levels. The knockdown of GPR65 by its siRNA restored osteoclastogenesis and decreased cAMP levels in the presence of psychosine.
  
  
  CONCLUSIONS
  Psychosine inhibits osteoclastogenesis by increasing intracellular cAMP levels via GPR65.
authors.affiliation: Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-2Dong, Songpa-Gu, Seoul, 138-736, South Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Ahn
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: J-E
authors.initials: JE
authors.lastname: Baek
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: S-Y
authors.initials: SY
authors.lastname: Park
authors.forename: Y-S
authors.initials: YS
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: B-J
authors.initials: BJ
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: J-M
authors.initials: JM
authors.lastname: Koh
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D011609:Psychosine / Q000494:pharmacology* / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: C513337:GPR65 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011609:Psychosine
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