Blockade of Endothelin Receptors Mitigates SARS-CoV-2-induced Osteochondral Damage

Previous studies have detected the presence of SARS-CoV-2 viral proteins in bronchial cartilage chondrocytes. We hypothesised that the leakage of viral proteins to local joint tissue was due to virus-induced endothelial dysfunction. Studies have also shown upregulation of endothelin-1 (ET-1), the most potent vasoconstrictor, in COVID patients. We are investigating the direct effect of SARS-CoV-2 spike protein (SP) and the host response to chondrocytes. Human mesenchymal stem cells (hMSCs)-differentiated chondrocytes were treated with either full-length SARS-CoV-2 spike protein (SP) only or a combination of spike protein, neutralising antibody to S1 and endothelin-1 (SAE) to mimic viral insult and host response respectively. RNA sequencing was performed to compared the change in transcriptome in control, SP and SAE. All samples were processed in the same batch. Default quality control parameters were used. Treatment (SP: 5 ug/mL SP, 24h; SAE: 5 ug/mL SP, 5 ug/mL neutralising antibody to S1 and 100nM ET-1, 24h) and control hMSCs-differentiated chondrocytes. Three replicates for each group. Samples are collected for bulk RNA seq.