Background
Abnormalities in apoptosis, cell cycle, and proliferation of human bone marrow mesenchymal stem cells (hBMSCs) significantly impact bone metabolism and remodeling, and thereby cause various skeletal disorders. Long-term exposure to a high dosage of dexamethasone (Dex) induces apoptosis and inhibits proliferation of mesenchymal stromal cells (MSCs), which are probably the primary causes of osteoporosis (OP) and steroid-induced osteonecrosis of the femoral head (SONFH). However, to date, the exact mechanisms of Dex-induced apoptosis of BMSCs are still poorly defined.
Methods
A microarray was used to identify differentially expressed lncRNA and mRNA in Dex-induced apoptosis of hBMSCs, and bioinformatics was used to further explore the role of these differentially expressed lncRNAs and mRNAs by the coding and noncoding (CNC) network. Furthermore, validation of the microarray results was performed by quantitative real-time PCR (qRT-PCR) analysis.
Results
The microarray analysis identified a total of 137 differentially expressed mRNA (90 up-regulated and 47 down-regulated) and 90 differentially expressed lncRNA (61 up-regulated and 29 down-regulated) in Dex-induced apoptosis of hBMSCs. The differentially expressed mRNA and lncRNA were associated with the regulation of cell apoptosis. Meanwhile, several signaling pathways involved in the regulation of cell apoptosis, including mTOR signaling pathway, Ras signaling pathway, HIF-1 signaling pathway, NF-kappa B signaling pathway, and TGF-beta signaling pathway, also were identified in interaction net of the significant pathways (Path-Net) analysis. Furthermore, the CNC network further identified 78 core regulatory genes involved in the regulation of apoptosis. Besides, validation by qRT-PCR of the key differentially expressed mRNA and lncRNA, reported to be closely related to cell apoptosis, confirmed the reliability of the microarray dataset.
Conclusions
Collectively, we utilized microarray to identify differentially expressed lncRNA and mRNA in Dex-induced apoptotic hBMSCs, and bioinformatics to explore the interaction between the differentially expressed genes. This study demonstrates the molecular mechanisms of Dex-induced apoptosis of hBMSCs and provides a new research direction for the study of the pathogenesis of steroid-induced osteonecrosis of femoral head.