Fatostatin, an SREBP inhibitor, prevented RANKL-induced bone loss by suppression of osteoclast differentiation

Biochimica Et Biophysica Acta
Kazuki Inoue, Yuuki Imai

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 nov...Continue Reading

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Citations

Aug 25, 2018·Oncogenesis·Viktor BrovkovychJonna Frasor
Jan 21, 2021·Cell Death and Differentiation·Zeyu ZhengJian Chen
Jan 13, 2021·Cells·Haemin KimKyung-Hyun Park-Min
Dec 31, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Cuilin LiZhi Li

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