Oxidative stress-related gene PRXL2A may participate in the occurrence and development of steroid-induced osteonecrosis of the femoral head by regulating osteoclast differentiation: A multi-omics analysis.

OBJECTIVES

Steroid-induced osteonecrosis of the femoral head (SIONFH) represents a global therapeutic challenge, and its pathogenesis requires in-depth investigation. While oxidative stress is recognized as a critical contributor to SIONFH, the underlying mechanism remains incompletely elucidated.

METHODS

In this study, multi-omics analysis of clinical specimens was performed to screen for oxidative stress-related molecules in SIONFH and identify hub molecules among them. Subsequently, the functional significance of these hub molecules was validated via Gene Ontology (GO) analysis and both in vitro and in vivo experiments. Furthermore, in vitro and in vivo experiments were conducted to further confirm the correlations between hub molecules, oxidative stress, and osteoclast differentiation.

RESULTS

RNA-seq analysis identified 1,107 differentially expressed genes, with PRXL2A designated as an oxidative stress-related hub gene. Subsequent protein DIA analysis detected 139 differentially expressed proteins, further confirming PRXL2A as an oxidative stress-associated hub protein. Functional exploration revealed that PRXL2A is involved in biological processes such as oxidative stress and osteoclast differentiation. When antioxidants were applied to osteoclasts, results from TRAP staining, RT-PCR, and other assays indicated that PRXL2A expression decreased with elevated oxidative stress and also declined as osteoclast differentiation increased. Finally, in vivo experiments further validated the negative correlations between PRXL2A, oxidative stress, and osteoclast differentiation.

CONCLUSION

This study demonstrates that enhanced oxidative stress in SIONFH patients reduces PRXL2A expression, which may promote osteoclast differentiation, thereby accelerating local femoral head bone destruction and contributing to SIONFH progression.