# Identification of osteoarthritis-related genes and potential drugs based on single cell RNA-seq data

## TL;DR

This study identifies genes linked to osteoarthritis and explores drugs like Pitavastatin that may help treat it.

## Contribution

The study introduces a novel approach combining single-cell RNA-seq data and drug prediction to identify OA-related genes and potential therapies.

## Key findings

- Five key genes (CXCL8, CCL20, MMP3, BIRC3, and ICAM1) were identified as related to osteoarthritis.
- Pitavastatin was found to reduce OA risk by inhibiting target genes like HMGCR and ITGAL.
- Cabazitaxel was shown to increase OA risk by inhibiting TUBB1 expression.

## Abstract

Osteoarthritis (OA) is a global problem that seriously affects human health. At present, there is still a lack of effective drugs to treat OA. Therefore, we need to find more drugs with preventive and therapeutic effects on OA. In this study, we obtained single-cell RNA sequencing (scRNA-seq) and bulk-RNA seq datasets from Gene Expression Omnibus (GEO). By using high-dimensional weighted correlation network analysis (hdWGCNA), random forest method and protein–protein interaction (PPI) network analyses, five key genes (CXCL8, CCL20, MMP3, BIRC3 and ICAM1) related to OA were identified and the RT-qPCR experiments verified the differential expression of CXCL8, CCL20 and BIRC3 between Triclocarban (TCC) treated zebrafishes and controls. The SAVERUNNER algorithm predicted 42 candidate drugs. Mendelian randomization (MR) of the candidate drugs showed that the increased expression of TUBB1 led to a reduced risk of OA (β = -0.08, P-value = 4.56E-04), while Cabazitaxel (a microtubule dynamics inhibitor commonly used in the treatment of advanced prostate cancer) inhibits the expression of TUBB1, thus increases the risk of OA. Pitavastatin (a statin lipid-lowering drug that can reduce blood lipid levels and the risk of cardiovascular diseases) target genes expression (for HMGCR \documentclass[12pt]{minimal}
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\begin{document}$$\upbeta$$\end{document}= 0.08, P-value = 6.57E-08) leads to an increased risk of OA, while Pitavastatin inhibits the expression of target genes, thus reduces risk of OA. The zebrafish experiments showed that Pitavastatin can increase the joint space of TCC treated OA zebrafish, while Cabazitaxel can decrease the joint space of TCC treated OA zebrafish. The RT-qPCR results of zebrafish verified that Pitavastatin inhibited the expression of HMGCR, while Cabazitaxel inhibited the expression of TUBB1. Our study suggested that Pitavastatin has therapeutic effects on OA, while Cabazitaxel increases the risk of OA.

The online version contains supplementary material available at 10.1186/s10020-025-01379-z.