Psychosine inhibits osteoclastogenesis and bone resorption via G protein-coupled receptor 65

被引:2
作者
Ahn, S. H. [1 ]
Lee, S. -Y. [2 ]
Baek, J. -E. [2 ]
Lee, S. -Y. [2 ]
Park, S. -Y. [2 ]
Lee, Y. -S. [2 ]
Kim, H. [1 ]
Kim, B. -J. [1 ]
Lee, S. H. [1 ]
Koh, J. -M. [1 ]
机构
[1] Univ Ulsan, Div Endocrinol & Metab, Asan Med Ctr, Coll Med, Seoul 138736, South Korea
[2] Asan Inst Life Sci, Seoul 138736, South Korea
关键词
cAMP; GPR65; Osteoclastogenesis; Psychosine; TWITCHER MOUSE; IN-VITRO; KINASE; TDAG8; DIFFERENTIATION; QUANTIFICATION; IDENTIFICATION; DISEASE; MODEL;
D O I
10.1007/s40618-015-0276-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background It was recently reported that G protein-coupled receptor 65 (GPR65) suppresses ovariectomy-induced bone loss. Aim 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. Conclusion Psychosine inhibits osteoclastogenesis by increasing intracellular cAMP levels via GPR65.
引用
收藏
页码:891 / 899
页数:9
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