Hepcidin基因敲除对小鼠骨代谢的影响及相关机制研究.docx

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Title: The Effects of Hepcidin Gene Knockout on Bone Metabolism in Mice and Its Underlying Mechanisms
Abstract:
Hepcidin, a key regulator of iron metabolism, has been recently implicated in the regulation of bone homeostasis. However, the exact consequences of hepcidin gene knockout on bone metabolism in mice and the underlying mechanisms remain unclear. In this study, we aimed to investigate the effects of hepcidin gene knockout on bone metabolism in mice and explore the related mechanisms.
Introduction:
Hepcidin is a hepatic peptide hormone that plays a crucial role in regulating iron homeostasis. It is primarily known for its ability to inhibit iron absorption in the intestine and iron release from macrophages, thereby controlling systemic iron levels. Over the past decade, growing evidence has suggested the involvement of hepcidin in bone metabolism. Emerging studies have shown that hepcidin may influence bone health directly through its action on osteoblasts and osteoclasts, as well as indirectly by affecting iron availability in the bone microenvironment. However, the precise effects of hepcidin gene knockout on bone metabolism and the underlying mechanisms are largely unclear.
Methods:
1. Generation of Hepcidin Gene Knockout Mice:
Hepcidin gene knockout mice were generated using CRISPR/Cas9 gene editing technology. The successful knockout was confirmed by genotyping and PCR analysis.
2. Evaluation of Bone Phenotype:
Bone phenotypes, including bone mineral density, bone architecture, and bone turnover markers, were assessed using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and enzyme-linked immunosorbent assays (ELISA), respectively.
3. Whole Transcriptome Analysis:
RNA-sequencing (RNA-seq) was performed on bone tissues from hepcidin knockout and wild-type mice to identify differentially expressed genes and pathways related to bone metabolism.
4. Quantitative Real-Time PCR (qRT-PCR):
qRT-PCR was conducted to validate the expression of selected genes of interest identified through RNA-seq analysis.
Results:
The hepcidin gene knockout mice exhibited alterations in bone phenotype characterized by decreased bone mineral density and compromised bone architecture. Furthermore, bone turnover markers revealed an increase in bone resorption and a decrease in bone formation in hepcidin knockout mice compared to wild-type mice. RNA-seq analysis of bone tissues revealed significant dysregulation of genes and pathways related to osteoblast and osteoclast differentiation, calcium signaling, and inflammatory responses.
Conclusion:
Taken together, our findings demonstrate that hepcidin gene knockout in mice leads to impaired bone metabolism characterized by reduced bone density, compromised architecture, and imbalanced bone turnover. The dysregulated expression of genes related to osteoblast and osteoclast differentiation, calcium signaling, and inflammation suggests potential mechanisms underlying the effects of hepcidin gene knockout on bone metabolism. Further investigation is warranted to elucidate the precise roles and signaling pathways involved in hepcidin-mediated regulation of bone homeostasis.
Keywords: Hepcidin, gene knockout, bone metabolism, osteoblast, osteoclast, iron homeostasis