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Journal of Orthopaedic Surgery and Research

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Open Access 01-12-2024 | Osteoporosis | Research article

Mechanism of Circ_HECW2 regulating osteoblast apoptosis in osteoporosis by attenuating the maturation of miR-1224-5p

Authors: Chao Zhang, Qiangqiang Li, Zhongduo Ye, Xiong Wang, Hui Zhao, Yongping Wang, Xingxing Zheng

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2024

Abstract

Background

Osteoporosis (OP) poses a significant clinical challenge with escalating morbidity. This study explores Circ_HECW2 expression in OP patients and its regulatory role in lipopolysaccharide (LPS)-induced osteoblast apoptosis.

Methods

Circ_HECW2 expression in OP patient serum and healthy controls was quantified using RT-qPCR. Diagnostic value of Circ_HECW2 for OP was assessed via ROC curve. Pearson’s correlation model examined associations between indicators. Human osteoblasts HFOB1.19, treated with LPS, were analyzed for Circ_HECW2, pre-miR-1224, miR-1224-5p, and PDK2 mRNA levels. TUNEL assay determined cell apoptosis and Western blot assessed cleaved-caspase-3 protein levels. RNase R resistance assay and actinomycin D assay confirmed Circ_HECW2’s cyclic structure. RNA pull-down and dual-luciferase reporter assay verified binding relationships between Circ_HECW2 and miR-1224 and between miR-1224-5p and PDK2.

Results

Circ_HECW2 exhibited elevated expression in OP patients with diagnostic significance and a negative correlation with lumbar T-score. LPS co-culture increased Circ_HECW2 expression in HFOB1.19 cells, significantly elevating apoptosis index and cleaved-caspase-3. Circ_HECW2 downregulation inhibited HFOB1.19 apoptosis, reduced pre-miR-1224 expression, and elevated mature miR-1224-5p. Circ_HECW2 bound to pre-miR-1224, and inhibiting miR-1224-5p reversed the effect of Circ_HECW2 downregulation on osteoblast apoptosis. miR-1224-5p targeted PDK2 transcription.

Conclusion

Circ_HECW2, highly expressed in OP, holds diagnostic significance and reflects disease severity. Circ_HECW2 reduces mature miR-1224-5p by binding to pre-miR-1224, upregulating PDK2, and facilitating LPS-induced osteoblast apoptosis.

Graphic Abstract

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Title: Mechanism of Circ_HECW2 regulating osteoblast apoptosis in osteoporosis by attenuating the maturation of miR-1224-5p
Authors: Chao Zhang
Qiangqiang Li
Zhongduo Ye
Xiong Wang
Hui Zhao
Yongping Wang
Xingxing Zheng
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Osteoporosis
Osteoporosis
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2024
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-023-04494-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mechanism of Circ_HECW2 regulating osteoblast apoptosis in osteoporosis by attenuating the maturation of miR-1224-5p

Abstract

Background

Methods

Results

Conclusion

Graphic Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Graphic Abstract

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