Dynamin‐related protein 1 positively regulates osteoclast differentiation and bone loss. Issue 1 (10th November 2020)

• Record Type: Journal Article
• Authors: Jeong, Sol; Seong, Ji Hye; Kang, Ju‐Hee; Lee, Dong‐Seok; Yim, Mijung
• Is Part Of: FEBS letters. Volume 595:Issue 1(2021)
• Page Start: 58
• Page End: 67
• Publication Date: 2020-11-10
• Subjects: bone loss -- DRP1 -- NFATc1 -- osteoclastogenesis -- RANKL; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13963
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Dynamin‐related protein 1 (DRP1) is a mitochondrial membrane GTPase and regulates mitochondrial fission. In this study, we found that the cytokine RANKL increased the expression of DRP1 and its receptor proteins, Fis1, Mid49, and Mid 51, during osteoclast formation in mouse bone marrow‐derived macrophages. Inactivation of the kinase GSK3β appeared to induce DRP1 expression. DRP1 knockdown or the DRP1 inhibitor Mdivi1 suppressed osteoclast differentiation via downregulation of c‐Fos and NFATc1, the key transcription factor for osteoclast formation. Finally, the DRP1 inhibitor suppressed lipopolysaccharide‐induced osteoclast formation in a calvarial model and ovariectomy‐induced bone loss in vivo . Taken together, our data demonstrate that DRP1 positively contributes to RANKL‐induced osteoclast differentiation by regulating the c‐Fos–NFATc1 axis, suggesting the importance of mitochondrial DRP1 in osteoclastogenesis. Abstract :