RRC ID 37903
著者 Inoue K, Imai Y.
タイトル Fatostatin, an SREBP inhibitor, prevented RANKL-induced bone loss by suppression of osteoclast differentiation.
ジャーナル Biochim Biophys Acta
Abstract Osteoclast differentiation is associated with both normal bone homeostasis and pathological bone diseases such as osteoporosis. Several transcription factors can regulate osteoclast differentiation, including c-fos and Nfatc1. Using genome-wide DNase-seq analysis, we found a novel transcription factor, SREBP2, that participates in osteoclast differentiation in vitro. Here, we asked whether SREBP2 actually plays a role in controlling bone metabolism in vivo. To answer this question, RAW264 cells, primary cultured osteoclasts and the mouse RANKL-induced bone loss model were treated with fatostatin, a small molecule inhibitor specific for the activation of SREBP. When cells were treated with fatostatin, osteoclast differentiation was impaired. Similar results were obtained following treatment with siRNA for Srebf2, the gene coding for SREBP2. In vivo, μCT analyses showed that fatostatin treatment preserved bone mass and structure in the proximal tibial trabecular bone in the mouse RANKL-induced bone loss model. In addition, bone histomorphometric analysis revealed that the protection of bone mass by fatostatin might have been achieved by suppression of RANKL-mediated osteoclast differentiation. These results indicated that the novel transcription factor SREBP2 physiologically functions in osteoclast differentiation in vivo and might be a possible therapeutic target for bone diseases.
巻・号 1852(11)
ページ 2432-41
公開日 2015-11-1
DOI 10.1016/j.bbadis.2015.08.018
PII S0925-4439(15)00255-0
PMID 26319416
IF 3.411
引用数 8
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126) RAW 264(RCB0535)