RIP140 in monocytes/macrophages regulates osteoclast differentiation and bone homeostasis

• DOI: 10.1172/jci.insight.90517
• Publication Date: 2017-04-07T02:24:53Z
• Authors: Bomi Lee; Urszula T. Iwaniec; Russell T. Turner; Yi-Wei Lin; Bart L. Clarke; Anne Gingery; Li-Na Wei
• Keywords: Monocyte; Bone remodeling

Osteolytic bone diseases, such as osteoporosis, are characterized by diminished quality and increased fracture risk. The therapeutic challenge remains to maintain homeostasis with a balance between osteoclast-mediated resorption osteoblast-mediated formation. Osteoclasts formed the fusion of monocyte/macrophage-derived precursors. Here we report, our knowledge for first time, that receptor-interacting protein 140 (RIP140) expression in osteoclast precursors its regulation crucial differentiation, activity, coupled In mice, monocyte/macrophage–specific knockdown RIP140 (mϕRIP140KD) resulted cancellous osteopenic phenotype significantly reduced Osteoclast isolated from mϕRIP140KD mice had differentiation potential. Furthermore, conditioned media primary cultures suppressed osteoblast differentiation. This suppressive activity was effectively rapidly terminated specific Syk-stimulated degradation. Mechanistic analysis revealed functions primarily inhibiting through forming transcription-suppressor complex testicular receptor 4 (TR4) repress osteoclastogenic genes. These data reveal monocyte/macrophage RIP140/TR4 complexes may serve critical transcription regulatory maintaining coupling Accordingly, propose potentially novel strategy, specifically targeting precursor osteolytic diseases.