Cellular and Molecular Connections Between Bone Fracture Healing and Exosomes

. 2023 Nov 28 ; 72 (5) : 565-574.

Jazyk angličtina Země Česko Médium print

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid38015756

Fracture healing is a multifaceted process that requires various phases and intercellular interactions. In recent years, investigations have been conducted to assess the feasibility of utilizing exosomes, small extracellular vesicles (EVs), to enhance and accelerate the healing process. Exosomes serve as a cargo transport platform, facilitating intercellular communication, promoting the presentation of antigens to dendritic cells, and stimulating angiogenesis. Exosomes have a special structure that gives them a special function, especially in the healing process of bone injuries. This article provides an overview of cellular and molecular processes associated with bone fracture healing, as well as a survey of existing exosome research in this context. We also discuss the potential use of exosomes in fracture healing, as well as the obstacles that must be overcome to make this a viable clinical practice.

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Irfan D, Ahmad I, Patra I, Margiana R, Rasulova MT, Sivaraman R, Kandeel M, et al. Stem cell-derived exosomes in bone healing: focusing on their role in angiogenesis. Cytotherapy. 2023;25:353–361. doi: 10.1016/j.jcyt.2022.08.008. PubMed DOI

Liao HT, Chen CT. Osteogenic potential: Comparison between bone marrow and adipose-derived mesenchymal stem cells. World J Stem Cells. 2014;6:288–295. doi: 10.4252/wjsc.v6.i3.288. PubMed DOI PMC

Pu X, Ma S, Gao Y, Xu T, Chang P, Dong L. Mesenchymal stem cell-derived exosomes: biological function and their therapeutic potential in radiation damage. Cells. 2020;10:42. doi: 10.3390/cells10010042. PubMed DOI PMC

Li W, Li L, Cui R, Chen X, Hu H, Qiu Y. Bone marrow mesenchymal stem cells derived exosomal Lnc TUG1 promotes bone fracture recovery via miR-22-5p/Anxa8 axis. Hum Cell. 2023;36:1041–1053. doi: 10.1007/s13577-023-00881-y. PubMed DOI PMC

Saxer F, Scherberich A, Todorov A, Studer P, Miot S, Schreiner S, Güven S, et al. Implantation of stromal vascular fraction progenitors at bone fracture sites: from a rat model to a first-in-man study. Stem Cells. 2016;34:2956–2966. doi: 10.1002/stem.2478. PubMed DOI

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7:1535750. doi: 10.1080/20013078.2018.1535750. PubMed DOI PMC

Hallal S, Tűzesi Á, Grau GE, Buckland ME, Alexander KL. Understanding the extracellular vesicle surface for clinical molecular biology. J Extracell Vesicles. 2022;11:e12260. doi: 10.1002/jev2.12260. PubMed DOI PMC

Greening DW, Xu R, Gopal SK, Rai A, Simpson RJ. Proteomic insights into extracellular vesicle biology - defining exosomes and shed microvesicles. Expert Rev Proteomics. 2017;14:69–95. doi: 10.1080/14789450.2017.1260450. PubMed DOI

Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013;126:5553–5565. doi: 10.1242/jcs.128868. PubMed DOI

Tauro BJ, Greening DW, Mathias RA, Mathivanan S, Ji H, Simpson RJ. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics. 2013;12:587–598. doi: 10.1074/mcp.M112.021303. PubMed DOI PMC

Xu R, Greening DW, Zhu HJ, Takahashi N, Simpson RJ. Extracellular vesicle isolation and characterization: toward clinical application. J Clin Invest. 2016;126:1152–1162. doi: 10.1172/JCI81129. PubMed DOI PMC

Kato T, Miyaki S, Ishitobi H, Nakamura Y, Nakasa T, Lotz MK, Ochi M. Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes. Arthritis Res Ther. 2014;16:R163. doi: 10.1186/ar4679. PubMed DOI PMC

Furuta T, Miyaki S, Ishitobi H, Ogura T, Kato Y, Kamei N, Miyado K, et al. Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model. Stem Cells Transl Med. 2016;5:1620–1630. doi: 10.5966/sctm.2015-0285. PubMed DOI PMC

Anderson HC, Garimella R, Tague SE. The role of matrix vesicles in growth plate development and biomineralization. Front Biosci. 2005;10:822–837. doi: 10.2741/1576. PubMed DOI

Wei J, Li H, Wang S, Li T, Fan J, Liang X, Li J, Han Q, et al. let-7 enhances osteogenesis and bone formation while repressing adipogenesis of human stromal/mesenchymal stem cells by regulating HMGA2. Stem Cells Dev. 2014;23:1452–1463. doi: 10.1089/scd.2013.0600. PubMed DOI PMC

Paschos NK. Editorial Commentary: Exosomes-a new word in the orthopaedic vocabulary? Arthroscopy. 2020;36:2229–2230. doi: 10.1016/j.arthro.2020.05.046. PubMed DOI

Yang Z, Zhang W, Ren X, Tu C, Li Z. Exosomes: a friend or foe for osteoporotic fracture? Front Endocrinol (Lausanne) 2021;12:679914. doi: 10.3389/fendo.2021.679914. PubMed DOI PMC

Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol. 1967;13:269–288. doi: 10.1111/j.1365-2141.1967.tb08741.x. PubMed DOI

Crescitelli R, Lässer C, Jang SC, Cvjetkovic A, Malmhäll C, Karimi N, Höög JL, et al. Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation. J Extracell Vesicles. 2020;9:1722433. doi: 10.1080/20013078.2020.1722433. PubMed DOI PMC

Tucher C, Bode K, Schiller P, Claßen L, Birr C, Souto-Carneiro MM, Blank N, et al. Extracellular vesicle subtypes released from activated or apoptotic T-lymphocytes carry a specific and stimulus-dependent protein cargo. Front Immunol. 2018;9:534. doi: 10.3389/fimmu.2018.00534. PubMed DOI PMC

Zhuo Z, Wang J, Luo Y, Zeng R, Zhang C, Zhou W, Guo K, et al. Targeted extracellular vesicle delivery systems employing superparamagnetic iron oxide nanoparticles. Acta Biomater. 2021;134:13–31. doi: 10.1016/j.actbio.2021.07.027. PubMed DOI

Abels ER, Breakefield XO. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016;36:301–312. doi: 10.1007/s10571-016-0366-z. PubMed DOI PMC

Vats S, Galli T. Role of SNAREs in unconventional secretion-focus on the VAMP7-dependent secretion. Front Cell Dev Biol. 2022;10:884020. doi: 10.3389/fcell.2022.884020. PubMed DOI PMC

Pužar Dominkuš P, Stenovec M, Sitar S, Lasič E, Zorec R, Plemenitaš A, Žagar E, et al. PKH26 labeling of extracellular vesicles: Characterization and cellular internalization of contaminating PKH26 nanoparticles. Biochim Biophys Acta Biomembr. 2018;1860:1350–1361. doi: 10.1016/j.bbamem.2018.03.013. PubMed DOI

Rozier P, Maumus M, Bony C, Maria ATJ, Sabatier F, Jorgensen C, Guilpain P, Noël D. Extracellular vesicles are more potent than adipose mesenchymal stromal cells to exert an anti-fibrotic effect in an in vitro model of systemic sclerosis. Int J Mol Sci. 2021;22:6837. doi: 10.3390/ijms22136837. PubMed DOI PMC

Buzás EI, Tóth E, Sódar BW, Szabó-Taylor K. Molecular interactions at the surface of extracellular vesicles. Semin Immunopathol. 2018;40:453–464. doi: 10.1007/s00281-018-0682-0. PubMed DOI PMC

Yun WS, Choi JS, Ju HM, Kim MH, Choi SJ, Oh ES, Seo YJ, Key J. Enhanced homing technique of mesenchymal stem cells using iron oxide nanoparticles by magnetic attraction in olfactory-injured mouse models. Int J Mol Sci. 2018;19:1376. doi: 10.3390/ijms19051376. PubMed DOI PMC

Huang X, Lan Y, Shen J, Chen Z, Xie Z. Extracellular vesicles in bone homeostasis: emerging mediators of osteoimmune interactions and promising therapeutic targets. Int J Biol Sci. 2022;18:4088–4100. doi: 10.7150/ijbs.69816. PubMed DOI PMC

Xiong Y, Chen L, Yan C, Zhou W, Yu T, Sun Y, Cao F, et al. M2 macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3. J Nanobiotechnology. 2020;18:66. doi: 10.1186/s12951-020-00622-5. PubMed DOI PMC

Zhang D, Wu Y, Li Z, Chen H, Huang S, Jian C, Yu A. MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1. J Nanobiotechnology. 2021;19:226. doi: 10.1186/s12951-021-00964-8. PubMed DOI PMC

Cui Y, Fu S, Sun D, Xing J, Hou T, Wu X. EPC-derived exosomes promote osteoclastogenesis through LncRNA-MALAT1. J Cell Mol Med. 2019;23:3843–3854. doi: 10.1111/jcmm.14228. PubMed DOI PMC

Chen L, Yu C, Xiong Y, Chen K, Liu P, Panayi AC, Xiao X, et al. Multifunctional hydrogel enhances bone regeneration through sustained release of Stromal Cell-Derived Factor-1α and exosomes. Bioact Mater. 2023;25:460–471. doi: 10.1016/j.bioactmat.2022.07.030. PubMed DOI PMC

Lin Z, Xiong Y, Meng W, Hu Y, Chen L, Chen L, Xue H, et al. Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant. Bioact Mater. 2022;13:300–311. doi: 10.1016/j.bioactmat.2021.10.042. PubMed DOI PMC

Zhang WL, Chi CT, Meng XH, Liang SD. miRNA-15a-5p facilitates the bone marrow stem cell apoptosis of femoral head necrosis through the Wnt/β-catenin/PPARγ signaling pathway. Mol Med Rep. 2019;19:4779–4787. doi: 10.3892/mmr.2019.10130. PubMed DOI PMC

Zhou J, Liu HX, Li SH, Gong Y-S, Zhou M-W, Zhang J-H, Zhu G-Y. Effects of human umbilical cord mesenchymal stem cells-derived exosomes on fracture healing in rats through the Wnt signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23:4954–4960. doi: 10.26355/eurrev_201906_18086. PubMed DOI

Zhao J, Li X, Hu J, Chen F, Qiao S, Sun X, Gao L, et al. Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization. Cardiovasc Res. 2019;115:1205–1216. doi: 10.1093/cvr/cvz040. PubMed DOI PMC

Jiang Y, Zhang J, Li Z, Jia G. Bone marrow mesenchymal stem cell-derived exosomal miR-25 regulates the ubiquitination and degradation of Runx2 by SMURF1 to promote fracture healing in mice. Front Med (Lausanne) 2020;7:577578. doi: 10.3389/fmed.2020.577578. PubMed DOI PMC

Wang R, Xu B, Xu H. TGF-β1 promoted chondrocyte proliferation by regulating Sp1 through MSC-exosomes derived miR-135b. Cell Cycle. 2018;17:2756–2765. doi: 10.1080/15384101.2018.1556063. PubMed DOI PMC

Sun H, Hu S, Zhang Z, Lun J, Liao W, Zhang Z. Expression of exosomal microRNAs during chondrogenic differentiation of human bone mesenchymal stem cells. J Cell Biochem. 2019;120:171–181. doi: 10.1002/jcb.27289. PubMed DOI

Shan SK, Lin X, Li F, Xu F, Zhong J-Y, Guo B, Wang Y, et al. Exosomes and bone disease. Curr Pharm Des. 2019;25:4536–4549. doi: 10.2174/1381612825666191127114054. PubMed DOI

Luo Z-W, Li F-X-Z, Liu Y-W, Rao S-S, Yin H, Huang J, Chen C-Y, et al. Aptamer-functionalized exosomes from bone marrow stromal cells target bone to promote bone regeneration. Nanoscale. 2019;11:20884–20892. doi: 10.1039/C9NR02791B. PubMed DOI

Li H, Liu D, Li C, Zhou S, Tian D, Xiao D, Zhang H, et al. Exosomes secreted from mutant-HIF-1α-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit. Cell Biol Int. 2017;41:1379–1390. doi: 10.1002/cbin.10869. PubMed DOI

Zhang D, Xiao W, Liu C, Wang Z, Liu Y, Yu Y, Jian C, Yu A. Exosomes derived from adipose stem cells enhance bone fracture healing via the activation of the Wnt3a/β-catenin signaling pathway in rats with type 2 diabetes mellitus. Int J Mol Sci. 2023;24:4852. doi: 10.3390/ijms24054852. PubMed DOI PMC

Zhang Y, Hao Z, Wang P, Xia Y, Wu J, Xia D, Fang S, Xu S. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif. 2019;52:e12570. doi: 10.1111/cpr.12570. PubMed DOI PMC

Zhang T, Jiang W, Liao F, Zhu P, Guo L, Zhao Z, Liu Y, et al. Identification of the key exosomal lncRNAs/mRNAs in the serum during distraction osteogenesis. J Orthop Surg Res. 2022;17:291. doi: 10.1186/s13018-022-03163-9. PubMed DOI PMC

Zhang L, Jiao G, Ren S, Zhang X, Li C, Wu W, Wang H, et al. Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion. Stem Cell Res Ther. 2020;11:38. doi: 10.1186/s13287-020-1562-9. PubMed DOI PMC

Wang X, Li X, Li J, Zhai L, Liu D, Abdurahman A, Zhang Y, et al. Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR-214-3p from bone marrow-derived mesenchymal stem cells. FASEB J. 2021;35:e21150. doi: 10.1096/fj.202001080RR. PubMed DOI PMC

Qi X, Zhang J, Yuan H, Xu Z, Li Q, Niu X, Hu B, et al. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats. Int J Biol Sci. 2016;12:836–849. doi: 10.7150/ijbs.14809. PubMed DOI PMC

Xie Y, Hu JH, Wu H, Huang ZZ, Yan HW, Shi ZY. Bone marrow stem cells derived exosomes improve osteoporosis by promoting osteoblast proliferation and inhibiting cell apoptosis. Eur Rev Med Pharmacol Sci. 2019;23:1214–1220. doi: 10.26355/eurrev_201902_17014. PubMed DOI

Qin Y, Wang L, Gao Z, Chen G, Zhang C. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci Rep. 2016;6:21961. doi: 10.1038/srep21961. PubMed DOI PMC

Li D, Liu J, Guo B, Liang C, Dang L, Lu C, He X, et al. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun. 2016;7:10872. doi: 10.1038/ncomms10872. PubMed DOI PMC

Xu R, Shen X, Si Y, Fu Y, Zhu W, Xiao T, Fu Z, et al. MicroRNA-31a-5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment. Aging Cell. 2018;17:e12794. doi: 10.1111/acel.12794. PubMed DOI PMC

Qin Y, Peng Y, Zhao W, Pan J, Ksiezak-Reding H, Cardozo C, Wu Y, et al. Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication. J Biol Chem. 2017;292:11021–11033. doi: 10.1074/jbc.M116.770941. PubMed DOI PMC

Xu Q, Cui Y, Luan J, Zhou X, Li H, Han J. Exosomes from C2C12 myoblasts enhance osteogenic differentiation of MC3T3-E1 pre-osteoblasts by delivering miR-27a-3p. Biochem Biophys Res Commun. 2018;498:32–37. doi: 10.1016/j.bbrc.2018.02.144. PubMed DOI

Aswad H, Jalabert A, Rome S. Depleting extracellular vesicles from fetal bovine serum alters proliferation and differentiation of skeletal muscle cells in vitro. BMC Biotechnol. 2016;16:32. doi: 10.1186/s12896-016-0262-0. PubMed DOI PMC

Matsuzaka Y, Tanihata J, Komaki H, Ishiyama A, Oya Y, Rüegg U, Takeda S-I, Hashido K. Characterization and functional analysis of extracellular vesicles and muscle-abundant miRNAs (miR-1, miR-133a, and miR-206) in C2C12 myocytes and mdx mice. PLoS One. 2016;11:e0167811. doi: 10.1371/journal.pone.0167811. PubMed DOI PMC

Lin Z, Xiong Y, Sun Y, Zeng R, Xue H, Hu Y, Chen L, et al. Circulating MiRNA-21-enriched extracellular vesicles promote bone remodeling in traumatic brain injury patients. Exp Mol Med. 2023;55:587–596. doi: 10.1038/s12276-023-00956-8. PubMed DOI PMC

Song H, Li X, Zhao Z, Qian J, Wang Y, Cui J, Weng W, et al. Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes. Nano Lett. 2019;19:3040–3048. doi: 10.1021/acs.nanolett.9b00287. PubMed DOI

Mi B, Chen L, Xiong Y, Yang Y, Panayi AC, Xue H, Hu Y, et al. Osteoblast/osteoclast and immune cocktail therapy of an exosome/drug delivery multifunctional hydrogel accelerates fracture repair. ACS Nano. 2022;16:771–782. doi: 10.1021/acsnano.1c08284. PubMed DOI

Sadvakassova G, Tiedemann K, Steer KJD, Mikolajewicz N, Stavnichuk M, In-Kyung Lee I, Sabirova Z, et al. Active hematopoiesis triggers exosomal release of PRDX2 that promotes osteoclast formation. Physiol Rep. 2021;9:e14745. doi: 10.14814/phy2.14745. PubMed DOI PMC

Farahat MN, Yanni G, Poston R, Panayi GS. Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 1993;52:870–875. doi: 10.1136/ard.52.12.870. PubMed DOI PMC

Charoenviriyakul C, Takahashi Y, Morishita M, Matsumoto A, Nishikawa M, Takakura Y. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics. Eur J Pharm Sci. 2017;96:316–322. doi: 10.1016/j.ejps.2016.10.009. PubMed DOI

Zhang C, Wang XY, Zhang P, He T-C, Han J-H, Zhang R, Lin J, et al. Cancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts. Cell Death Dis. 2022;13:57. doi: 10.1038/s41419-022-04506-4. PubMed DOI PMC

Liu W, Li L, Rong Y, Qian D, Chen J, Zhou Z, Lu Y, et al. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater. 2020;103:196–212. doi: 10.1016/j.actbio.2019.12.020. PubMed DOI

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