铁调素水平与骨代谢相关性临床及实验研究

Clinical and experimental studies on the correlation between hepcidin level and bone metabolism

目的探讨人群血清铁调素浓度与骨密度的相关性,并了解铁调素对小鼠成骨前体细胞(MC3T3-E1)分化影响及相关机制。方法①采用酶联免疫吸附法(ELISA)检测骨量正常与骨质疏松症两组人群血清铁调素水平;②采用细胞计数试剂检测比较成骨前体细胞(MC3T3-E1)在不同浓度铁调素干预后细胞增殖的影响,运用RT-PCR、Western Blot方法了解铁调素对成骨分化功能指标(ALP、Runx2、BMP2、P-SMAD1/5和SMAD5)影响。结果人群血清铁调素水平与腰椎、髋部骨密度呈显著正相关;铁调素在一定浓度范围(0~10 ng/mL)浓度增加可显著上调细胞功能分化表达(ALP、Runx2)、促进成骨信号通路蛋白表达(BMP2、P-SMAD1/5和SMAD5)。结论临床数据显示血清铁调素水平和骨量具有显著相关性,铁调素水平低骨密度值也低;而细胞实验显示一定浓度铁调素可显著激活BMP2-SMAD1/5信号通路、上调成骨分化相关基因的表达,诱导细胞成骨分化。因此,本研究结果提示:血清铁调素可能与骨质疏松症存在相关性,临床检测铁调素可能是骨质疏松症诊疗过程中一种新的评估指标,值得进一步研究。

Objective To explore the correlation between serum hepcidin concentration and bone density in the population,and to understand the effect of hepcidin on the differentiation of mouse osteoblast precursor cells(MC3T3-E1)and its related mechanisms.Methods①Enzyme linked immunosorbent assay(ELISA)was used to detect serum hepcidin levels in two groups of people with normal bone mass and osteoporosis;②Using cell counting reagents to detect and compare the effects of osteogenic precursor cells(MC3T3-E1)on cell proliferation after intervention with different concentrations of hepcidin RT-PCR and Western Blot method were used to investigate the effects of hepcidin on osteogenic differentiation functional indicators(ALP,Runx2,BMP2,P-SMAD1/5,and SMAD5).Results There was a significant positive correlation between serum hepcidin levels and bone mineral density of the lumbar spine and hip in the population;An increase in the concentration of hepcidin within a certain range(0-10 ng/mL)can significantly upregulate the expression of cell functional differentiation(ALP,Runx2)and promote the expression of osteogenic signaling pathway proteins(BMP2,P-SMAD1/5,and SMAD5).Conclusion Clinical data shows a significant correlation between serum hepcidin levels and bone mass,with low hepcidin levels and low bone density values;Cell experiments have shown that a certain concentration of hepcidin can significantly activate the BMP2-SMAD1/5 signaling pathway,upregulate the expression of osteogenic differentiation related genes,and induce cell osteogenic differentiation;Therefore,this study suggests that serum hepcidin may be correlated with osteoporosis,and clinical detection of hepcidin may be a new evaluation indicator for the diagnosis and treatment of osteoporosis,which is worth further research.