Journal Article

Osteogenic effect of bone marrow mesenchymal stem cell-derived exosomes on steroid-induced osteonecrosis of the femoral head

Li, Yongfeng, Fang, Shanhong, Chen, Peng

2019

Overview

Animal studies have demonstrated the therapeutic effect of mesenchymal stem cells (MSCs) on osteogenesis, but little is known about the functions of exosomes (Exos) released by bone MSCs (BMSCs). Here, we investigated the effect of BMSC Exos on steroid-induced femoral head necrosis (SFHN) and explored the vital genes involved in this process. BMSCs were isolated from healthy and SFHN rats. BMSC Exos were isolated using the Exosome Precipitation Kit and characterized by transmission electron microscopy and Western blotting. SFHN BMSCs were incubated with Exos from healthy BMSCs. Osteogenic ability was assessed by oil red O staining and alizarine red staining. Differentially expressed genes (DEGs) induced by Exos were screened using the Osteogenesis RT2 Profiler PCR Array. The effect of upregulated was examined using lentivirus-mediated siRNA. The results revealed that BMSC Exos were 100-150 nm in size and expressed CD63. Moreover, BMSC Exo-treated SFHN cells exhibited suppressed adipogenesis compared to model cells. PCR array showed that eleven and nine genes were upregulated and downregulated, respectively, in the BMSC Exo-treated SFHN cells compared to the model group. Among the DEGs, osteogenesis-related genes, including , , , , and , may play important roles in SFHN. Furthermore, the DEGs were mainly involved in immune response, osteoblast differentiation, and in the transforming growth factor-β/bone morphogenetic protein signaling pathway. The level of the SOX9 protein was upregulated by Exos, and silencing significantly decreased the osteogenic effect of BMSC Exos. Our data suggest that Exos derived from BMSCs mainly affect SFHN osteogenesis, and this finding can be further investigated to develop a novel therapeutic agent for SFHN.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove Medical Press
• Subject: Adipocytes / Adipogenesis / Animals / Biocompatibility / Biotechnology / Bone growth / Bone marrow / bone marrow mesenchymal stem cells / Bone morphogenetic protein 2 / Bone Morphogenetic Protein 2 - genetics / Bone Morphogenetic Protein 2 - metabolism / Bone morphogenetic protein 6 / Bone Morphogenetic Protein 6 - genetics / Bone Morphogenetic Protein 6 - metabolism / Bone Morphogenetic Protein Receptors, Type I - genetics / Bone Morphogenetic Protein Receptors, Type I - metabolism / Bone morphogenetic proteins / Bone surgery / CD63 antigen / Cells, Cultured / Chemical compounds / Dexamethasone - toxicity / Exosome / Exosomes / Exosomes - metabolism / Exosomes - ultrastructure / Femur / Femur Head Necrosis - chemically induced / Femur Head Necrosis - metabolism / Femur Head Necrosis - physiopathology / Femur Head Necrosis - therapy / Gelatinase B / Gene expression / Gene Expression Regulation / Gene Regulatory Networks / Genes / Growth factors / Health aspects / Immune response / Immune system / Ischemia / Joint surgery / Kinases / Matrix Metalloproteinase 9 - genetics / Matrix Metalloproteinase 9 - metabolism / Membranes / Mesenchymal stem cells / Mesenchymal Stem Cells - metabolism / Mesenchymal Stem Cells - ultrastructure / Mesenchyme / Original Research / Osteoblastogenesis / Osteogenesis / Osteonecrosis / ostosis / Pathogenesis / Penicillin / Pharmacology / Proteins / Signal Transduction / siRNA / Sox9 protein / SOX9 Transcription Factor - genetics / SOX9 Transcription Factor - metabolism / Staining / Stem cell transplantation / Stem cells / steroid-induced femoral head necrosis / Steroids / Substance abuse treatment / Transcription factors / Transforming growth factor-b / Transmission electron microscopy / Western blotting