||Monday,1 August 2016, 16:00～
|| Seminar-shitsu 1, IDAC Research building 7F
|| Multiple Myeloma-derived exosomes inhibit osteoblast differentiation
||Institute of Biomedical Sciences, Tokushima University
|| Yohei Hayashi（Cell Resource Center for Biomedical Research・ext.8572）
||Multiple Myeloma (MM) is a plasma cell cancer that causes bone destruction. Exosomes are cell-derived small vesicles and contribute to cell-cell communication. We found that MM-derived exosomes suppress osteoblast differentiation. Bone morphogenic protein 2 (BMP2) treatment increase osteoblast markers expression in osteoblastic precursor cell MC3T3-E1. MM-derived exosomes suppressed osteoblast marker expression in BMP2-treated MC3T3-E1. BMP2 activates Smad signaling pathway and directly up-regulates dlx5 gene expression during osteoblast differentiation. In BMP2-treated MC3T3-E1, MM-derived exosomes suppressed dlx5 gene promoter activity and mRNA expression. MM-derived exosomes did not change Smad phosphorylation nor nuclear translocation. These results suggest that MM-derived exosomes suppress osteoblast differentiation by inhibiting Smad activity in nuclear compartment. It is poorly known about MM-derived exosome’s function and how osteoblasts are controlled by exosomes. Our findings will provide new therapeutic targets for multiple myeloma and bone diseases.