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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., Competing Interests: No competing financial interests exist and the authors report no conflicts of interest for this work., (© 2021 Hao et al.)

Steroid‐induced osteonecrosis of the femoral head (SIONFH) has been a common disease following corticosteroid therapy. Presently, we aim to explore the functions of circular RNA (circ) PVT1 in SIONFH rats and the underlying mechanism. Glucocorticoid (GC) was used to treat SD rats and bone marrow‐derived mesenchymal stem cells (BMSCs) to construct SIONFH model in vitro and in vivo, respectively. The pathological injury of the femoral head in the SIONFH rats was detected via haematoxylin‐eosin (HE) staining and immunohistochemistry (IHC). The osteogenic differentiation, proliferation and apoptosis of BMSCs were detected. Western blot was used to detect Smad7, Bax, Bcl2 and Smad2/3. The potential targets of circPVT1 and miR‐21‐5p were validated through luciferase reporter gene assay and RNA pull‐down assay, respectively. We found that CircPVT1 was decreased in the femoral head of SIONFH rats and GC‐treated BMSCs, while miR‐21‐5p was markedly up‐regulated. Overexpressed circPVT1 attenuated the apoptosis and cell viability inhibition of BMSCs induced by GC, while miR‐21‐5p up‐regulation had the opposite effects. What's more, the in vivo experiments confirmed that up‐regulating circPVT1 repressed osteonecrosis in SIONFH rats through repressing apoptosis. Mechanistically, circPVT1 functioned as a ceRNA of miR‐21‐5p, which targeted at the 3'untranslated region of Smad7. CircPVT1 enhancing Smad7 and mitigating GC activated TGFβ/Smad2/3 pathway through inhibiting miR‐21‐5p. In conclusion, CircPVT1 exerts protective effects against SIONFH via modulating miR‐21‐5p‐mediated Smad7/TGFβ pathway. [ABSTRACT FROM AUTHOR]