Gene expression profiling of peripheral blood in patients with steroid-induced osteonecrosis of the femoral head

Abstract

Aim: Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe complication following glucocorticoid therapy. This study aimed to identify the differential mRNA expression and investigate the molecular mechanisms of SONFH. Materials & methods: RNA sequencing was performed in eight SONFH patients, five non-SONFH patients and five healthy individuals. Results: A total of 1555, 3997 and 5276 differentially expressed mRNAs existed between the following combinations: SONFH versus non-SONFH, SONFH versus healthy subjects and non-SONFH versus healthy subjects. Increased ISM1 expression might contribute to a high risk of SONFH through antiangiogenesis. Decreased FOLR3 expression might affect the metabolism of homocysteine, leading to avascular necrosis of the femoral head. KCNJ2, which plays a pivotal role in regulating bone development, was also deregulated. Conclusion: ISM1, FOLR3 and KCNJ2 might be related to the occurrence of SONFH.

Summary points

Background

• Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe complication in clinical practice following extensive steroid treatment for various diseases.

• The occurrence of SONFH in patients using high-dose/long-term glucocorticoids has individual variability, which indicates that molecular biomarkers are urgently needed for the prevention of SONFH.

Materials & methods

• RNA sequencing was performed to identify differentially expressed mRNAs in peripheral blood samples from eight SONFH patients, five non-SONFH patients and five healthy individuals.

• Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyze underlying mechanisms.

Results

• A total of 1555, 3997 and 5276 differentially expressed mRNAs existed between the combinations SONFH versus non-SONFH group, SONFH versus healthy subjects and non-SONFH versus healthy subjects.

• Compared with the non-SONFH group, the most enriched Gene Ontology terms for the SONFH group were concentrated in dendrites, dendritic trees, voltage-gated calcium channel complexes, neutrophil degranulation, neutrophil-mediated immunity and neutrophil activation involved in the immune response membrane.

• Differentially expressed mRNAs were closely associated with ribosome, circadian entrainment and oxytocin signaling pathways in the comparison between SONFH and non-SONFH subjects based on Kyoto Encyclopedia of Genes and Genomes analysis.

• Of these top differentially expressed genes, we suggest that three key genes, ISM1, FOLR3 and KCNJ2, might be associated with the occurrence and development of SONFH.

Conclusion

• Our results may provide novel insights into the pathogenesis of and intervention for SONFH. Large-scale studies and verification experiments are necessary to confirm the present results.

Keywords: :

• differentially expressed gene
• functional enrichment analysis
• glucocorticoids
• RNA sequencing
• steroid-induced osteonecrosis of the femoral head

Financial disclosure

This work was supported by grants from the Medical Science and Technology Project of Henan Province (LHGJ20190269) and the National Key Research and Development Program of China (2020YFC2008304). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with an interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by grants from the Medical Science and Technology Project of Henan Province (LHGJ20190269) and the National Key Research and Development Program of China (2020YFC2008304). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.