Magnesium-containing bioceramics stimulate exosomal miR-196a-5p secretion to promote senescent osteogenesis through targeting Hoxa7/MAPK signaling axis  

作　　者：Lei Qi Xin Fang Jinge Yan Cancan Pan Weiwen Ge Jing Wang Steve GF.Shen Kaili Lin Lei Zhang 

机构地区：[1]Department of Oral&Cranio-Maxillofacial Surgery,Shanghai Ninth People’s Hospital,College of Stomatology,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,PR China [2]National Clinical Research Center for Oral Diseases,Shanghai,200011,PR China [3]Shanghai Key Laboratory of Stomatology&Shanghai Research Institute of Stomatology,Shanghai,200011,PR China [4]Shanghai University of Medicine and Health Sciences,Shanghai,201318,PR China

出　　处：《Bioactive Materials》2024年第3期14-29,共16页生物活性材料（英文）

基　　金：support National Natural Science Foundation of China(No.81970973);Science and Technology Commission of Shanghai Municipality(No.20ZR1432200,21140900102,21490711700,22010502600);Disciplinary Characteristic Biobank Project of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(No.YBKB202110);Cross Disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai JiaoTong University School of Medicine(No.JYJC202219);Shanghai’s Top Priority Research Center(No.2022ZZ01017);CAMS Innovation Fund for Medical Sciences(No.CIFMS,2019-I2M-5-037).

摘　　要：Stem cell senescence is characterized by progressive functional dysfunction and secretory phenotypic changes including decreased proliferation,dysfunction of osteogenic and angiogenic differentiation,increased secretion of the senescence-associated secretory phenotype(SASP),which bring difficulties for bone repair.Rescuing or delaying senescence of aged bone marrow mesenchymal stem cells(O-BMSCs)was considered as effective strategy for bone regeneration in aging microenvironment.Magnesium(Mg)ion released from bioceramics was reported to facilitate bone regeneration via enhancing osteogenesis and alleviating senescence.In this study,Akermanite biocreamics(Akt)containing Mg ion as a model was demonstrated to promote osteogenesis and angiogenesis effects of O-BMSCs by activating the MAPK signaling pathway in vitro.Moreover,the enhanced osteogenesis effects might be attributed to enhanced Mg-containing Akt-mediated exosomal miR-196a-5p cargo targeting Hoxa7 and activation of MAPK signaling pathway.Furthermore,the in vivo study confirmed that 3D-printed porous Mg-containing Akt scaffolds effectively increased bone regeneration in cranial defects of aged rats.The current results indicated that the exosomal-miR-196a-5p/Hoxa7/MAPK signaling axis might be the potential mechanism underlying Akt-mediated osteogenesis.The exosome-meditaed therapy stimulated by the released Mg ion contained in Akt biocreamics or other biomaterials might serve as a candidate strategy for bone repair in aged individuals.

关 键 词：MAGNESIUM AKERMANITE Senescent osteogenesis Exosomal miR-196a-5p Hoxa7/MAPK axis 

分 类 号：R318[医药卫生—生物医学工程]