Acid sphingomyelinase regulates osteoclastogenesis by modulating sphingosine kinases downstream of RANKL signaling

被引：10

作者：

Bao, Xilinqiqige ^{[1
]}

Ogawa, Takuya ^{[1
]}

Se, Satoru ^{[1
]}

Akiyama, Motofusa ^{[1
]}

Bahtiar, Anton ^{[1
]}

Takeya, Tatsuo ^{[1
]}

Ishida-Kitagawa, Norihiro ^{[1
]}

机构：

[1] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300192, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 405卷 / 04期

关键词：

Acid sphingomyelinase; Sphingosine kinase; Ceramide; c-Fos; NFAT2; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; 1-PHOSPHATE; EXPRESSION; NFAT2; DIFFERENTIATION; ACTIVATION; CELLS;

D O I：

10.1016/j.bbrc.2011.01.061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acid sphingomyelinase (ASM) was identified as a gene induced by NFAT2 activation in osteoclasts. Suppression of ASM expression in bone marrow macrophages by knockdown enhanced c-Fos/NFAT2 expression, increasing the number of TRAP-positive multinucleated cells in vitro. SphK1 was upregulated during the late stage of osteoclastogenesis, while SphK2 expression remained constant. SphK1 was downregulated following ASM knockdown, while SphK2 levels were unchanged. Experiments using shRNA and catalytically-inactive form demonstrated inhibitory and stimulatory activities on osteoclast formation of SphK1 and SphK2, respectively. These results suggest that ASM regulates osteoclastogenesis by modulating the balance between SphK1 and SphK2 downstream of RANKL signaling. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：533 / 537

页数：5

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