Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19.

Background: Corona Virus Disease 2019 (COVID-19) and Osteoarthritis (OA) are diseases that seriously affect the physical and mental health and life quality of patients, particularly elderly patients. However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients. Methods: The four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockTools. Results: Firstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2. Conclusion: In the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2.

Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and osteoarthritis.

A growing of evidence has showed that patients with osteoarthritis (OA) had a higher coronavirus 2019 (COVID-19) infection rate and a poorer prognosis after infected it. Additionally, scientists have also discovered that COVID-19 infection might cause pathological changes in the musculoskeletal system. However, its mechanism is still not fully elucidated. This study aims to further explore the sharing pathogenesis of patients with both OA and COVID-19 infection and find candidate drugs. Gene expression profiles of OA (GSE51588) and COVID-19 (GSE147507) were obtained from the Gene Expression Omnibus (GEO) database. The common differentially expressed genes (DEGs) for both OA and COVID-19 were identified and several hub genes were extracted from them. Then gene and pathway enrichment analysis of the DEGs were performed; protein-protein interaction (PPI) network, transcription factor (TF)-gene regulatory network, TF-miRNA regulatory network and gene-disease association network were constructed based on the DEGs and hub genes. Finally, we predicted several candidate molecular drugs related to hub genes using DSigDB database. The receiver operating characteristic curve (ROC) was applied to evaluate the accuracy of hub genes in the diagnosis of both OA and COVID-19. In total, 83 overlapping DEGs were identified and selected for subsequent analyses. CXCR4, EGR2, ENO1, FASN, GATA6, HIST1H3H, HIST1H4H, HIST1H4I, HIST1H4K, MTHFD2, PDK1, TUBA4A, TUBB1 and TUBB3 were screened out as hub genes, and some showed preferable values as diagnostic markers for both OA and COVID-19. Several candidate molecular drugs, which are related to the hug genes, were identified. These sharing pathways and hub genes may provide new ideas for further mechanistic studies and guide more individual-based effective treatments for OA patients with COVID-19 infection.

"Lessons from Rare Forms of Osteoarthritis".

Osteoarthritis (OA) is one of the most prevalent conditions in the world, particularly in the developed world with a significant increase in cases and their predicted impact as we move through the twenty-first century and this will be exacerbated by the covid pandemic. The degeneration of cartilage and bone as part of this condition is becoming better understood but there are still significant challenges in painting a complete picture to recognise all aspects of the condition and what treatment(s) are most appropriate in individual causes. OA encompasses many different types and this causes some of the challenges in fully understanding the condition. There have been examples through history where much has been learnt about common disease(s) from the study of rare or extreme phenotypes, particularly where Mendelian disorders are involved. The often early onset of symptoms combined with the rapid and aggressive pathogenesis of these diseases and their predictable outcomes give an often-under-explored resource. It is these "rarer forms of disease" that William Harvey referred to that offer novel insights into more common conditions through their more extreme presentations. In the case of OA, GWAS analyses demonstrate the multiple genes that are implicated in OA in the general population. In some of these rarer forms, single defective genes are responsible. The extreme phenotypes seen in conditions such as Camptodactyly Arthropathy-Coxa Vara-pericarditis Syndrome, Chondrodysplasias and Alkaptonuria all present potential opportunities for greater understanding of disease pathogenesis, novel therapeutic interventions and diagnostic imaging. This review examines some of the rarer presenting forms of OA and linked conditions, some of the novel discoveries made whilst studying them, and findings on imaging and treatment strategies.