Identifying the Potential Differentially Expressed miRNAs and mRNAs in Osteonecrosis of the Femoral Head Based on Integrated Analysis

Abstract

Purpose

Osteonecrosis of the femoral head is a common disease of the hip that leads to severe pain or joint disability. We aimed to identify potential differentially expressed miRNAs and mRNAs in osteonecrosis of the femoral head.

Methods

The data of miRNA and mRNA were firstly downloaded from the database. Secondly, the regulatory network of miRNAs–mRNAs was constructed, followed by function annotation of mRNAs. Thirdly, an in vitro experiment was applied to validate the expression of miRNAs and targeted mRNAs. Finally, GSE123568 dataset was used for electronic validation and diagnostic analysis of targeted mRNAs.

Results

Several regulatory interaction pairs between miRNA and mRNAs were identified, such as hsa-miR-378c-WNT3A/DACT1/CSF1, hsa-let-7a-5p-RCAN2/IL9R, hsa-miR-28-5p-RELA, hsa-miR-3200-5p-RELN, and hsa-miR-532-5p-CLDN18/CLDN10. Interestingly, CLDN10, CLDN18, CSF1, DACT1, IL9R, RCAN2, RELN, and WNT3A had the diagnostic value for osteonecrosis of the femoral head. Wnt signaling pathway (involved WNT3A), chemokine signaling pathway (involved RELA), focal adhesion and ECM-receptor interaction (involved RELN), cell adhesion molecules (CAMs) (involved CLDN18 and CLDN10), cytokine–cytokine receptor interaction, and hematopoietic cell lineage (involved CSF1 and IL9R) were identified.

Conclusion

The identified differentially expressed miRNAs and mRNAs may be involved in the pathology of osteonecrosis of the femoral head.

Keywords:

• osteonecrosis of the femoral head
• miRNAs
• mRNAs
• signaling pathway

Acknowledgment

This study was funded by the Department of Science and Technology of Shanxi Provincial of “The mechanism of Tongluoshenggu Decoction in the treatment of steroid-induced femoral head necrosis based on autophagy mediated by PI3K/Akt/mTOR signaling pathway” (2020SF-287).

Abbreviations

CLDN10, claudin 10; CLDN18, claudin 18; CSF1, colony stimulating factor 1; COX2, cyclooxygenase 2; DACT1, dishevelled binding antagonist of beta catenin 1; RELN, reelin; CAMs, cell adhesion molecules; FGF2, fibroblast growth factor 2; GEO, Gene Expression Omnibus database; HIF2, hypoxic induction factor 2; IGF1, insulin-like growth factor 1; IL9R, interleukin 9 receptor; MMP9, matrix metalloproteinases 9; NOS2, nitric oxide synthase 2; RCAN2, regulator of calcineurin 2; SOX9, SRY-box transcription factor 9; VEGF, vascular endothelial growth factor; WNT3A, Wnt family member 3A.

Disclosure

No competing financial interests exist and the authors report no conflicts of interest for this work.