Drug Design, Development and Therapy (Oct 2020)
Osteogenic Effect of tsRNA-10277-Loaded Exosome Derived from Bone Mesenchymal Stem Cells on Steroid-Induced Osteonecrosis of the Femoral Head
Abstract
Shanhong Fang,1,* Tianmin He,2,* Jiarun Jiang,3 Yongfeng Li,1 Peng Chen1 1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 3Department of Orthopedics, The Hospital of Changle District, Fuzhou 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng ChenDepartment of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Taijiang District, Fuzhou 350005, People’s Republic of ChinaEmail [email protected]: Steroids are known to inhibit osteogenic differentiation and subsequent bone formation in bone mesenchymal stem cells (BMSCs). However, little is known about the role of BMSC exosomes (Exos) and tRNA-derived small RNAs (tsRNAs) in steroid-induced osteonecrosis of the femoral head (SONFH). The objective of this study was to characterize the tsRNA expression profiles of plasma Exos collected from SONFH patients and healthy individuals using small RNA sequencing and further explore the effect of BMSC Exos carrying specific tsRNAs on osteogenic differentiation.Materials and Methods: Based on insights from small RNA sequencing, five differentially expressed (DE) tsRNAs were selected for quantitative real-time polymerase chain reaction (qRT-PCR). The regulatory networks associated with interactions of the tsRNAs-mRNA-pathways were reconstructed. The osteogenesis and adipogenesis in BMSCs were detected via ALP and oil red O staining methods, respectively.Results: A total of 345 DE small RNAs were screened, including 223 DE tsRNAs. The DE tsRNAs were enriched in Wnt signaling pathway and osteogenic differentiation. We identified five DE tsRNAs, among which tsRNA-10277 was significantly downregulated in plasma Exos of SONFH patients compared to that in healthy individuals. Dexamethasone-induced BMSCs were associated with an increased fraction of lipid droplets and decreased osteogenic differentiation, whereas BMSC Exos restored the osteogenic differentiation of that. After treatment of tsRNA-10277-loaded BMSC Exos, the lipid droplets and osteogenic differentiation ability were found to be decreased and enhanced in dexamethasone-induced BMSCs, respectively.Conclusion: An altered tsRNA profile might be involved in the pathophysiology of SONFH. tsRNA-10277-loaded BMSC Exos enhanced osteogenic differentiation ability of dexamethasone-induced BMSCs. Our results provide novel insights into the osteogenic effect of BMSC Exos carrying specific tsRNAs on SONFH.Keywords: steroid-induced femoral head necrosis, small RNA sequencing, tsRNA-10277, BMSC exosomes, osteogenic differentiation
