不同来源外泌体对骨骼发育及骨骼疾病的影响

doi:10.11843/j.issn.0366-6964.2024.02.001

摘要/Abstract

摘要： 在骨骼发育过程中,骨骼是通过膜内成骨和软骨内成骨两种不同的成骨机制形成的,软骨内骨化是长骨发育的第二阶段,生长板是机体进行软骨内骨化的场所,生长板软骨细胞受损会破坏软骨内成骨的进程,严重抑制骨骼发育或产生骨骼疾病。外泌体是由膜的双层内陷形成,具有脂质双分子层的细胞外囊泡,可以包裹蛋白质、脂质和核酸(非编码RNA、mRNA)等,作用于靶细胞从而发挥细胞间通讯的关键作用。外泌体作为近年来研究的热点,有大量研究发现其与骨骼发育、骨骼疾病的发生和治疗关系密切。因此,本文主要综述了不同来源外泌体对骨骼发育和骨骼疾病的影响,梳理了不同来源外泌体对骨骼的调控作用,为探究不同来源外泌体在畜禽骨骼发育与骨骼疾病方面的预防和治疗提供理论依据。

关键词: 外泌体, 不同来源, 骨骼疾病, 骨骼发育

Abstract: In the process of bone development, bones are formed by intramembranous osteogenesis and endochondral osteogenesis, endochondral ossification is the second stage of long bone development, growth plate is the body for intrachondral ossification, growth plate chondrocytes damaged will destroy the process of intrachondral osteogenesis, seriously inhibit bone development or produce bone diseases. Exosomes are formed by the bilayer invagination of the membrane, and extracellular vesicles with lipid bilayers can envelop proteins, lipids, and nucleic acids (non-coding RNA, mRNA), etc., acting on target cells to play a key role in intercellular communication. Exosomes have been the focus of research in recent years, and a large number of studies have found that they are closely related to bone development and the occurrence and treatment of bone diseases. Therefore, this article mainly reviews the effects of exosomes from different sources on bone development and bone diseases, and sorts out the regulatory effects of exosomes from different sources on bone, so as to provide a theoretical basis for exploring the prevention and treatment of exosomes from different sources in the development of livestock and poultry bones and bone diseases.

Key words: exosomes, different sources, bone diseases, bone development

中图分类号:

S852.2

刘新新, 周恩友, 安智远, 蔡春霞, 张露洁, 李建增, 李转见, 闫峰宾, 康相涛, 高延玲, 韩瑞丽. 不同来源外泌体对骨骼发育及骨骼疾病的影响[J]. 畜牧兽医学报, 2024, 55(2): 419-426.

LIU Xinxin, ZHOU Enyou, AN Zhiyuan, CAI Chunxia, ZHANG Lujie, LI Jianzeng, LI Zhuanjian, YAN Fengbin, KANG Xiangtao, GAO Yanling, HAN Ruili. Effects of Exosomes from Different Sources on Bone Development and Bone Diseases[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(2): 419-426.

参考文献

[1] 奚晓娥,徐峥,李放,等.大骨鸡和AA+肉鸡骨骼性状差异及BMP2 mRNA表达研究[J].畜牧与兽医,2023,55(2):11-17.
XI X E,XU Z,LI F,et al.Study on the difference in bone traits and the expression of BMP2 mRNA between Dagu chicken and AA+ broiler[J].Animal Husbandry & Veterinary Medicine,2023,55(2):11-17.(in Chinese)
[2] CHAROENNGAM N,NASR A,SHIRVANI A,et al.Hereditary metabolic bone diseases:a review of pathogenesis,diagnosis and management[J].Genes (Basel),2022,13(10):1880.
[3] SZAFRANIEC G M,SZELESZCZUK P,DOLKA B.Review on skeletal disorders caused by Staphylococcus spp. in poultry[J].Vet Quart,2022,42(1):21-40.
[4] GURUNATHAN S,KANG M H,KIM J H.A comprehensive review on factors influences biogenesis,functions,therapeutic and clinical implications of exosomes[J].Int J Nanomed,2021,16:1281-1312.
[5] CAI G F,CAI G L,ZHOU H C,et al.RETRACTED ARTICLE:mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction[J].Stem Cell Res Ther,2021,12(1):2.
[6] PHU T A,NG M,VU N K,et al.IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity[J].Mol Ther,2022,30(6):2274-2297.
[7] SONG H Y,LI X Q,ZHAO Z C,et al.Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes[J].Nano Lett,2019,19(5):3040-3048.
[8] WANG S Y,SHI Y.Exosomes derived from immune cells:the new role of tumor immune microenvironment and tumor therapy[J].Int J Nanomed,2022,17:6527-6550.
[9] ZHANG Y M,CAI Z C,SHEN Y L,et al.Hydrogel-load exosomes derived from dendritic cells improve cardiac function via Treg cells and the polarization of macrophages following myocardial infarction[J].J Nanobiotechnol,2021,19(1):271.
[10] SONG Y F,WANG M F,TONG H,et al.Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression[J].Oncogene,2021,40(3):633-646.
[11] LIU Y,ZENG Y,SI H B,et al.Exosomes derived from human urine-derived stem cells overexpressing miR-140-5p alleviate knee osteoarthritis through downregulation of VEGFA in a rat model[J].Am J Sports Med,2022,50(4):1088-1105.
[12] CAI J,GONG L Q,LI G D,et al.Exosomes in ovarian cancer ascites promote epithelial-mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p[J].Cell Death Dis,2021,12(2):210.
[13] KIM K U,KIM W H,JEONG C H,et al.More than nutrition:therapeutic potential of breast milk-derived exosomes in cancer[J].Int J Mol Sci,2020,21(19):7327.
[14] MURDICA V,GIACOMINI E,ALTERI A,et al.Seminal plasma of men with severe asthenozoospermia contain exosomes that affect spermatozoa motility and capacitation[J].Fertil Steril,2019,111(5):897-908.e2.
[15] JOHNSTONE R M,ADAM M,HAMMOND J R,et al.Vesicle formation during reticulocyte maturation.Association of plasma membrane activities with released vesicles (exosomes)[J].J Biol Chem,1987,262(19):9412-9420.
[16] 郭马娣,赵娟,黄小义.以外泌体为基础的液体活检在胰腺癌诊断中的研究进展[J].肿瘤防治研究,2022,49(3):240-245.
GUO M D,ZHAO J,HUANG X Y.Research progress of exosome-based liquid biopsy in diagnosis of pancreatic cancer[J].Cancer Research on Prevention and Treatment,2022,49(3):240-245.(in Chinese)
[17] KALLURI R,LEBLEU V S.The biology,function,and biomedical applications of exosomes[J].Science,2020,367(6478):eaau6977.
[18] 李竹君,王晨羽,龙笑.间充质干细胞在整形美容领域的应用[J].协和医学杂志,2022,13(3):370-376.
LI Z J,WANG C Y,LONG X.Application of mesenchymal stem cells in plastic and cosmetic surgery[J].Medical Journal of Peking Union Medical College Hospital,2022,13(3):370-376.(in Chinese)
[19] KOK V C,YU C C.Cancer-derived exosomes:their role in cancer biology and biomarker development[J].Int J Nanomed,2020,15:8019-8036.
[20] ZHOU Y J,ZHANG Y,GONG H,et al.The role of exosomes and their applications in cancer[J].Int J Mol Sci,2021,22(22):12204.
[21] QIN Y H,SUN R X,WU C L,et al.Exosome:a novel approach to stimulate bone regeneration through regulation of osteogenesis and angiogenesis[J].Int J Mol Sci,2016,17(5):712.
[22] 王泽华,张丽昀,马春燕.间充质干细胞来源细胞外囊泡对肺部疾病作用研究进展[J].中国生物工程杂志,2023,43(5):76-84.
WANG Z H,ZHANG L Y,MA C Y.Research progress on the role of mesenchymal stem cell extracellular vesicles in lung diseases[J].China Biotechnology,2023,43(5):76-84.(in Chinese)
[23] CHEN P F,ZHENG L,WANG Y Y,et al.Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration[J].Theranostics,2019,9(9):2439-2459.
[24] WANG Z K,WU Y M,ZHAO Z H,et al.Study on transorgan regulation of intervertebral disc and extra-skeletal organs through exosomes derived from bone marrow mesenchymal stem cells[J].Front Cell Dev Biol,2021,9:741183.
[25] ZHANG Y,CAO X Y,LI P F,et al.MicroRNA-935-modified bone marrow mesenchymal stem cells-derived exosomes enhance osteoblast proliferation and differentiation in osteoporotic rats[J].Life Sci,2021,272:119204.
[26] DOYLE E C,WRAGG N M,WILSON S L.Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis[J].Knee Surg Sports Traumatol Arthrosc,2020,28(12):3827-3842.
[27] 秦威城,尚奇,张鹏,等."脾肾相关"理论探讨脂肪源性外泌体在老年性骨质疏松症中的研究进展[J].中国骨质疏松杂志,2023,29(2):277-281.
QIN W C,SHANG Q,ZHANG P,et al.Research progress of adipose derived exocrine body in senile osteoporosis based on the spleen-kidney relation theory[J].Chinese Journal of Osteoporosis,2023,29(2):277-281.(in Chinese)
[28] 唐骜,舒晴,贾绍辉,等.脂肪间充质干细胞外泌体改善骨质疏松症的研究进展[J].中国骨质疏松杂志,2023,29(5):707-712.
TANG A,SHU Q,JIA S H,et al.Advances in the treatment of osteoporosis by adipose mesenchymal stem cell exosomes[J].Chinese Journal of Osteoporosis,2023,29(5):707-712.(in Chinese)
[29] HONG P Y,YANG H,WU Y,et al.The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells:a comprehensive review[J].Stem Cell Res Ther,2019,10(1):242.
[30] KANG Y,XU C,MENG L A,et al.Exosome-functionalized magnesium-organic framework-based scaffolds with osteogenic, angiogenic and anti-inflammatory properties for accelerated bone regeneration[J].Bioact Mater,2022,18:26-41.
[31] 王宪峰,王锟,孙晗,等.脐带间充质干细胞外泌体LncRNA H19修复软骨损伤的机制[J].中国组织工程研究,2024,28(1):20-25.
WANG X F,WANG K,SUN H,et al.Mechanism underlying exosomal lncRNA H19 derived from umbilical cord mesenchymal stem cells promotes cartilage injury repair[J].Chinese Journal of Tissue Engineering Research,2024,28(1):20-25.(in Chinese)
[32] 顾亚,李毅,陈铭,等.不同细胞来源外泌体在骨质疏松小鼠体内的骨靶向性比较[J].解放军医学院学报,2021,42(3):310-314.
GU Y,LI Y,CHEN M,et al.Comparison of bone targeting properties of exosomes from different cell sources in osteoporotic mice[J].Academic Journal of Chinese PLA Medical School,2021,42(3):310-314.(in Chinese)
[33] WANG Q,SHEN X F,CHEN Y,et al.Osteoblasts-derived exosomes regulate osteoclast differentiation through miR-503-3p/Hpse axis[J].Acta Histochem,2021,123(7):151790.
[34] LYU H,XIAO Y,GUO Q,et al.The role of bone-derived exosomes in regulating skeletal metabolism and extraosseous diseases[J]. Front Cell Dev Biol,2020,8:89.
[35] YANG J X,XIE P,LI Y S,et al.Osteoclast-derived miR-23a-5p-containing exosomes inhibit osteogenic differentiation by regulating Runx2[J].Cell Signal,2020,70:109504.
[36] 孙硕,张锡光,岳乔宁,等.外泌体携载微小RNA治疗骨关节炎的研究[J].中国骨质疏松杂志,2023,29(2):248-251.
SUN S,ZHANG X G,YUE Q N,et al.Research progress of exosome by carrying microRNA in the treatment of osteoarthritis[J].Chinese Journal of Osteoporosis,2023,29(2):248-251.(in Chinese)
[37] PAJARINEN J,LIN T,GIBON E,et al.Mesenchymal stem cell-macrophage crosstalk and bone healing[J].Biomaterials,2019, 196:80-89.
[38] 齐永强.肝癌细胞外泌体来源miR-6756-3p诱导破骨细胞分化的机制研究[D].武汉:华中科技大学,2020.
QI Y Q.The mechanism of tumor-derived exosomal miR-6756-3p induces osteoclasts differentiation[D].Wuhan:Huazhong University of Science and Technology,2020.(in Chinese)
[39] YANG R Z,XU W N,ZHENG H L,et al.Exosomes derived from vascular endothelial cells antagonize glucocorticoid-induced osteoporosis by inhibiting ferritinophagy with resultant limited ferroptosis of osteoblasts[J].J Cell Physiol,2021,236(9):6691-6705.
[40] 余昌敏,张丹,闵明,等.外泌体miRNA作为癌症早期诊断标志物的研究进展[J].中国免疫学杂志,2020, 36(22):2786-2790.
YU C M,ZHANG D,MIN M,et al.Research progress of exosomes miRNA as biomarkers for early diagnosis in cancer[J].Chinese Journal of Immunology,2020,36(22):2786-2790.(in Chinese)
[41] 陈晓峰,王开元,梁芳铭,等.外泌体递药系统及其在肿瘤治疗中的应用[J].化学进展,2022,34(4):773-786.
CHEN X F,WANG K Y,LIANG F M,et al.Exosomes drug delivery systems and their application in tumor treatment[J].Progress in Chemistry,2022,34(4):773-786.(in Chinese)
[42] 陈长军,赵鑫,陈李毅乐,等.外泌体在骨代谢及骨、关节疾病诊治中的研究进展[J].重庆医科大学学报,2021,46(5):610-617.
CHEN C J,ZHAO X,CHEN L Y L,et al.Progress of exosomes in bone metabolism,and diagnosis and treatment of bone and joint diseases[J].Journal of Chongqing Medical University,2021,46(5):610-617.(in Chinese)
[43] 缪海冰,陈真.血浆外泌体miRNA-204-5p和类风湿关节炎[J].中华临床免疫和变态反应杂志,2022,16(3):314-318.
MIAO H B,CHEN Z.Plasma exosome miR-204-5p and rheumatoid arthritis[J].Chinese Journal of Allergy & Clinical Immunology,2022,16(3):314-318.(in Chinese)
[44] 黄双霜,向小娜,余曦,等.富血小板血浆来源外泌体治疗膝骨关节炎的机制与作用[J].中国组织工程研究,2023,27(15):2420-2426.
HUANG S S,XIANG X N,YU X,et al.Mechanism and effect of platelet-rich plasma-derived exosomes for treating knee osteoarthritis[J].Chinese Journal of Tissue Engineering Research,2023,27(15):2420-2426.(in Chinese)
[45] 陆益花.老年女性骨质疏松相关血浆外泌体miRNA筛选及功能机制研究[D].苏州:苏州大学,2019.
LU Y H.Screening and functional mechanism of MicroRNAs in plasma exosomes associated with osteoporosis in elderly women[D].Suzhou:Soochow University,2019.(in Chinese)
[46] DONG B J,LIU X H,LI J W,et al.Berberine encapsulated in exosomes derived from platelet-rich plasma promotes chondrogenic differentiation of the bone marrow mesenchymal stem cells via the Wnt/β-catenin pathway[J].Biol Pharm Bull,2022,45(10):1444-1451.
[47] DU Y,TANG H Y,GU X,et al.Radiation can regulate the expression of miRNAs associated with osteogenesis and oxidation in exosomes from peripheral blood plasma[J].Oxid Med Cell Longev,2021,2021:6646323.
[48] LIU X J,YUAN J H,WU Z W,et al.Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis[J].J Nanobiotechnol,2023,21(1):94.
[49] CHUNG I M,RAJAKUMAR G,VENKIDASAMY B,et al.Exosomes:current use and future applications[J].Clin Chim Acta,2020,500:226-232.
[50] 康圆博,王思凡,陈婷君,等.外泌体的研究进展及其法医学意义[J].法医学杂志,2022,38(6):754-762.
KANG Y B,WANG S F,CHEN T J,et al.Research progress of exosomes and their forensic significance[J].Journal of Forensic Medicine,2022,38(6):754-762.(in Chinese)
[51] 李鸿鸣,廖海蓉.乳源性外泌体减少新生儿肠道损伤[J].当代医学,2022,28(7):189-191.
LI H M,LIAO H R.Milk-derived exosomes reduce neonatal intestinal injury[J].Contemporary Medicine,2022,28(7):189-191.(in Chinese)
[52] 王银妃,曾思洁,盛晓静.母乳miRNA对婴儿生理功能发育的影响研究进展[J].医学研究生学报,2022,35(5):555-560.
WANG Y F,ZENG S J,SHENG X J.Research progress on effects of breast milk miRNA on physiological function development of infants[J].Journal of Medical Postgraduates,2022,35(5):555-560.(in Chinese)
[53] 宋思嘉,陈文霞,李贤玉.人唾液外泌体对大鼠皮肤损伤的修复作用[J].口腔颌面外科杂志,2022,32(3):152-157.
SONG S J,CHEN W X,LI X Y.Repair effects of human saliva-derived exosomes on cutaneous wound healing:an experimental study in rats[J].Journal of Oral and Maxillofacial Surgery,2022,32(3):152-157.(in Chinese)
[54] 童远武,董方,李艳莉,等.复发性阿弗他口腔溃疡患者唾液外泌体miR-142-5p、FOXO3表达的相关性研究[J].疑难病杂志,2023,22(6):640-645.
TONG Y W,DONG F,LI Y L,et al.Correlation[LL]study on the expression of miR-142-5p and FOXO3 in saliva exosomes of RAU patients[J].Chinese Journal of Difficult and Complicated,2023,22(6):640-645.(in Chinese)
[55] 徐英娇,王姗.唾液外泌体在口腔鳞状细胞癌的研究进展[J].口腔医学,2022,42(7):664-667,672.
XU Y J,WANG S.Research progress on the role of salivary exosomes in oral squamous cell carcinoma[J].Stomatology, 2022,42(7):664-667,672.(in Chinese)
[56] BASKARAN S,PANNER SELVAM M K,AGARWAL A.Exosomes of male reproduction[J].Adv Clin Chem,2020,95:149-163.
[57] NAZRI H M,IMRAN M,FISCHER R,et al.Characterization of exosomes in peritoneal fluid of endometriosis patients[J].Fertil Steril,2020,113(2):364-373.e2.
[58] 丁凯泽,余蕾,黄智,等.唐氏综合征胎儿羊水外泌体miRNA差异表达谱分析[J].南方医科大学学报,2022,42(2):293-299.
DING K Z,YU L,HUANG Z,et al.Differential expression profile of miRNAs in amniotic fluid exosomes from fetuses with Down syndrome[J].Journal of Southern Medical University,2022,42(2):293-299.(in Chinese)
[59] 武长贤.汗液外泌体和外膜囊泡对布鲁氏菌胞内侵染的作用研究[D].武汉:华中农业大学,2020.
WU C X.The effect and regulatory mechanism of sweat exosome and outer membrane vesicle in Brucella intracellular survival[D].Wuhan:Huazhong Agricultural University,2020.(in Chinese)