Identification of ubiquitination-related biomarkers in osteoarthritis: Combining transcriptome and Mendelian...

Osteoarthritis is the predominant joint ailment. Multiple studies demonstrate that the dysregulation of catalytic regulators of ubiquitination and deubiquitination disrupts cartilage imbalance, consequently facilitating the advancement of osteoarthritis.

Ubiquitination-related biomarkers for osteoarthritis were found by differential expression, weighted gene co-expression network analysis, Mendelian randomization, Receiver Operating Characteristic curves, and expression analyses. Subsequently, an examination of immune infiltration was conducted to evaluate the contrasting immunological circumstances between osteoarthritis and controls. Additionally, single-cell analysis was employed to screen key cell types, and analyze the expression of biomarkers during their differentiation. The expression of biomarkers was subsequently validated using real time quantitative polymerase chain reaction.

CBLB and NQO2 were determined as biomarkers, having risk effects on osteoarthritis (odd ratio > 1). Analysis of immune infiltration indicated a significant disparity in the number of 15 immune cell types between osteoarthritis and control groups, such as type 2 T helper cells and macrophages, and two biomarkers showed opposite associations with these immune cells. Single-cell analysis annotated seven cell types, with prehypertrophic chondrocytes as the key cells. Notably, two biomarkers had expression early and late stages during prehypertrophic chondrocytes differentiation. Finally, experiments analysis indicated that CBLB decreased and NQO2 increased in osteoarthritis samples.

CBLB and NQO2 were biomarkers associated with ubiquitination that exert causal effects on osteoarthritis. These findings provide potential therapeutic targets for clinical intervention and help to personalize treatment for osteoarthritis patients.