SLC40A1通过铁代谢调控BMSC成骨分化在骨质疏松症中的作用  

Roles of SLC40A1 in regulating iron metabolism and osteogenic differentiation of BMSC in the pathogenesis of osteoporosis

作　　者：李明宇 方宇[1] 董重阳 LI Mingyu;FANG Yu;DONG Chongyang(Department of Orthopaedics,Afiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China;School of Traditional Chinese Medicine,Inner Mongolia Medical University,Hohhot 010107,China)

机构地区：[1]内蒙古医科大学附属医院骨科,呼和浩特010050 [2]内蒙古医科大学中医学院,呼和浩特010107

出　　处：《生命的化学》2025年第2期213-222,共10页Chemistry of Life

基　　金：内蒙古自治区自然科学基金项目(2022MS08058);内蒙古自治区高等学校科学研究项目(NJZZ22614);内蒙古医科大学联合项目(YKD2021LH005);内蒙古医科大学笃学人才扶持计划项目(ZY20243117);内蒙古医科大学附属医院博士科研启动基金项目(2022NYFYBS003);内蒙古自治区卫生健康科技计划项目(202202160);内蒙古医学科学院公立医院科研联合基金项目(2024GLLH0274)。

摘　　要：骨质疏松症是一种以骨量减少、骨结构破坏和骨折风险增加为特征的慢性疾病,对社会和医疗体系构成重大负担。近年来,铁代谢失调与骨健康之间的联系逐渐受到关注。特别是SLC40A1基因编码的铁转运蛋白Ferroportin 1在调节铁离子的细胞内外运输中发挥了关键作用,对骨骼代谢有潜在影响,主要表现在铁的过度积累会引发氧化应激。这一过程通过调控多种信号通路(如Wnt/β-catenin通路)抑制骨髓间充质干细胞(bone marrow mesenchymal stem cell,BMSC)的成骨分化,并促进脂肪生成。此外,铁过载通过诱导内质网应激、激活MAPK和NF-κB等途径,进一步影响成骨细胞的功能。而SLC40A1在铁的转运过程中起着关键作用,其表达水平的变化能够直接影响细胞内铁的积累,从而调节BMSC的骨代谢功能。高表达SLC40A1通常伴随着铁流出增加,减少铁蓄积,反之则可能促进骨质疏松的发生。本文旨在探讨铁蓄积、SLC40A1表达与BMSC成骨分化之间的联系,为后续进一步探究骨质疏松症的机制及其治疗提供新的思路和见解。Osteoporosis is a chronic disease characterized by loss of bone mass,deterioration of bone structure and an increased risk of fracture,which places a significant burden on society and healthcare systems.In recent years,the link between dysregulated iron metabolism and bone health has received increasing attention.Ferroportin 1,an iron transport protein encoded by the SLC40A1 gene,plays a central role in regulating the intra-and extracellular transport of iron ions,with potential implications for bone metabolism.Iron overload primarily induces oxidative stress,which inhibits the osteogenic differentiation of bone marrow mesenchymal stem cell(BMSC)and promotes adipogenesis through the modulation of various signaling pathways,such as the Wnt/β-catenin pathway.In addition,iron overload further disrupts osteoblast function by inducing ER stress and activating MAPK and NF-κB signaling pathways.While SLC40A1 is critical to iron transport,changes in its expression can directly influence intracellular iron accumulation,thereby regulating bone metabolism in BMSC.High expression of SLC40A1 is typically associated with increased iron efflux and decreased iron accumulation,whereas decreased expression may contribute to the development of osteoporosis.This review aims to explore the relationship between iron accumulation,SLC40A1 expression and osteogenic differentiation of BMSC,providing new insights into the mechanisms underlying osteoporosis and potential strategies for its treatment.

关 键 词：SLC40A1 骨质疏松 铁蓄积 BMSC 铁转运蛋白 

分 类 号：R580[医药卫生—内分泌]