{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:01:20Z","timestamp":1792184480374,"version":"4.4.0"},"reference-count":110,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Natural Science Foundation","award":["2022NSCQMSX1032"],"award-info":[{"award-number":["2022NSCQMSX1032"]}]},{"name":"Chongqing Natural Science Foundation","award":["cquchkfjj007"],"award-info":[{"award-number":["cquchkfjj007"]}]},{"name":"Chongqing Natural Science Foundation","award":["KJQN202300125"],"award-info":[{"award-number":["KJQN202300125"]}]},{"name":"Key Laboratory Development Foundation of Affiliated Cancer Hospital of Chongqing University","award":["2022NSCQMSX1032"],"award-info":[{"award-number":["2022NSCQMSX1032"]}]},{"name":"Key Laboratory Development Foundation of Affiliated Cancer Hospital of Chongqing University","award":["cquchkfjj007"],"award-info":[{"award-number":["cquchkfjj007"]}]},{"name":"Key Laboratory Development Foundation of Affiliated Cancer Hospital of Chongqing University","award":["KJQN202300125"],"award-info":[{"award-number":["KJQN202300125"]}]},{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["2022NSCQMSX1032"],"award-info":[{"award-number":["2022NSCQMSX1032"]}]},{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["cquchkfjj007"],"award-info":[{"award-number":["cquchkfjj007"]}]},{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["KJQN202300125"],"award-info":[{"award-number":["KJQN202300125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and biological signaling pathways. Bone regeneration consists of a series of coordinated osteoconductive and osteoinductive biological processes. As mediators of intercellular communication, EVs can promote bone regeneration by regulating osteoblast-mediated bone formation, osteoclast-mediated bone resorption, and other pathways. This review summarizes the biogenesis of EVs and the mechanisms by which EV-mediated intercellular communication promotes bone regeneration. Additionally, we focus on the research progress of EVs in various diseases related to bone regeneration. Finally, based on the above research, we explore the clinical applications of engineered EVs in the diagnosis and treatment of bone regeneration-related diseases.<\/jats:p>","DOI":"10.3390\/cimb46090548","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T13:38:41Z","timestamp":1724765921000},"page":"9269-9285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Extracellular Vesicles in Bone Regeneration and Associated Bone Diseases"],"prefix":"10.3390","volume":"46","author":[{"given":"Xinyue","family":"Wan","sequence":"first","affiliation":[{"name":"School of Medicine, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7303-6176","authenticated-orcid":false,"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University, Chongqing 400030, China"},{"name":"Department of Bone and Soft Tissue Oncology, Chongqing University Cancer Hospital,  Chongqing University School of Medicine, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2100719","DOI":"10.1002\/advs.202100719","article-title":"Injectable Affinity and Remote Magnetothermal Effects of Bi-Based Alloy for Long-Term Bone Defect Repair and Analgesia","volume":"8","author":"He","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17059","DOI":"10.1038\/boneres.2017.59","article-title":"Bone biomaterials and interactions with stem cells","volume":"5","author":"Gao","year":"2017","journal-title":"Bone Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00198-018-4704-5","article-title":"European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"30","author":"Kanis","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2121106","DOI":"10.1001\/jamanetworkopen.2021.21106","article-title":"Prevalence of Osteoporosis and Fracture in China: The China Osteoporosis Prevalence Study","volume":"4","author":"Wang","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/jcpe.13058","article-title":"Bone grafts: Which is the ideal biomaterial?","volume":"46","author":"Haugen","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ivanov, A.A., Kuznetsova, A.V., Popova, O.P., Danilova, T.I., and Yanushevich, O.O. (2021). Modern Approaches to Acellular Therapy in Bone and Dental Regeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413454"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41590-021-00899-0","article-title":"Extracellular vesicles in immunomodulation and tumor progression","volume":"22","author":"Marar","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.addr.2020.04.004","article-title":"Extracellular vesicles as drug delivery systems: Why and how?","volume":"159","author":"Elsharkasy","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12144","DOI":"10.1002\/jev2.12144","article-title":"A brief history of nearly EV-erything-The rise and rise of extracellular vesicles","volume":"10","author":"Couch","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2023.01.057","article-title":"Biomimetic synthesis and optimization of extracellular vesicles for bone regeneration","volume":"355","author":"Song","year":"2023","journal-title":"J. Control Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12964-021-00806-y","article-title":"Small extracellular vesicles: From mediating cancer cell metastasis to therapeutic value in pancreatic cancer","volume":"20","author":"Zhang","year":"2022","journal-title":"Cell Commun. Signal"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12943-018-0897-7","article-title":"Effect of exosomal miRNA on cancer biology and clinical applications","volume":"17","author":"Sun","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12943-019-0991-5","article-title":"Exosomes: Composition, biogenesis, and mechanisms in cancer metastasis and drug resistance","volume":"18","author":"Mashouri","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.ymthe.2023.02.013","article-title":"Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading","volume":"31","author":"Gupta","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41580-023-00576-0","article-title":"Context-specific regulation of extracellular vesicle biogenesis and cargo selection","volume":"24","author":"Dixson","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.semcdb.2015.02.010","article-title":"Extracellular vesicles in cancer: Exosomes, microvesicles and the emerging role of large oncosomes","volume":"40","author":"Minciacchi","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12943-019-0973-7","article-title":"Microvesicles and chemokines in tumor microenvironment: Mediators of intercellular communications in tumor progression","volume":"18","author":"Bian","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12964-023-01251-9","article-title":"Advances in biological functions and applications of apoptotic vesicles","volume":"21","author":"Zou","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7439","DOI":"10.1038\/ncomms8439","article-title":"A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure","volume":"6","author":"Tixeira","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1242\/jcs.02959","article-title":"A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation","volume":"119","author":"Moss","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41418-019-0342-5","article-title":"ROCK1 but not LIMK1 or PAK2 is a key regulator of apoptotic membrane blebbing and cell disassembly","volume":"27","author":"Tixeira","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.7150\/ijbs.69816","article-title":"Extracellular Vesicles in Bone Homeostasis: Emerging Mediators of Osteoimmune Interactions and Promising Therapeutic Targets","volume":"18","author":"Huang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1089\/ten.teb.2016.0463","article-title":"Collagen Membrane and Immune Response in Guided Bone Regeneration: Recent Progress and Perspectives","volume":"23","author":"Chu","year":"2017","journal-title":"Tissue Eng. Part. B Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ekstr\u00f6m, K., Omar, O., Gran\u00e9li, C., Wang, X., Vazirisani, F., and Thomsen, P. (2013). Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075227"},{"key":"ref_27","first-page":"206","article-title":"A multifunctional neuromodulation platform utilizing Schwann cell-derived exosomes orchestrates bone microenvironment via immunomodulation, angiogenesis and osteogenesis","volume":"23","author":"Hao","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, Z., Wang, Y., Li, S., and Li, Y. (2021). Exosomes Derived From M2 Macrophages Facilitate Osteogenesis and Reduce Adipogenesis of BMSCs. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.680328"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"C621","DOI":"10.1152\/ajpcell.00228.2013","article-title":"Extracellular membrane vesicles as a mechanism of cell-to-cell communication: Advantages and disadvantages","volume":"306","author":"Turturici","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1634\/stemcells.2007-0197","article-title":"Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing","volume":"25","author":"Chamberlain","year":"2007","journal-title":"Stem Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jht.2011.08.003","article-title":"Specialized connective tissue: Bone, the structural framework of the upper extremity","volume":"25","author":"Weatherholt","year":"2012","journal-title":"J. Hand Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nri2395","article-title":"Mesenchymal stem cells in health and disease","volume":"8","author":"Uccelli","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pankajakshan, D., and Agrawal, D.K. (2014). Mesenchymal Stem Cell Paracrine Factors in Vascular Repair and Regeneration. J. Biomed. Technol. Res., 1.","DOI":"10.19104\/jbtr.2014.107"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.jss.2012.04.070","article-title":"Bone marrow mesenchymal stem cells ameliorate hepatic ischemia\/reperfusion injuries via inactivation of the MEK\/ERK signaling pathway in rats","volume":"178","author":"Pan","year":"2012","journal-title":"J. Surg. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1182\/blood.V99.10.3838","article-title":"Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli","volume":"99","author":"Magni","year":"2002","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1002\/stem.2369","article-title":"Mesenchymal Stromal Cells Induce Peculiar Alternatively Activated Macrophages Capable of Dampening Both Innate and Adaptive Immune Responses","volume":"34","author":"Chiossone","year":"2016","journal-title":"Stem Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.4049\/jimmunol.1300194","article-title":"TSG-6 inhibits neutrophil migration via direct interaction with the chemokine CXCL8","volume":"192","author":"Dyer","year":"2014","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/stem.2575","article-title":"Concise Review: MSC-Derived Exosomes for Cell-Free Therapy","volume":"35","author":"Phinney","year":"2017","journal-title":"Stem Cells"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.actbio.2020.12.046","article-title":"Exosomes from TNF-\u03b1-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss","volume":"122","author":"Nakao","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, D., Cao, H., Hua, W., Gao, L., Yuan, Y., Zhou, X., and Zeng, Z. (2022). Mesenchymal Stem Cell-Derived Extracellular Vesicles for Bone Defect Repair. Membranes, 12.","DOI":"10.3390\/membranes12070716"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Qin, Y., Wang, L., Gao, Z., Chen, G., and Zhang, C. (2016). Bone marrow stromal\/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci. Rep., 6.","DOI":"10.1038\/srep21961"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wang, X., Omar, O., Vazirisani, F., Thomsen, P., and Ekstr\u00f6m, K. (2018). Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193059"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41580-020-00279-w","article-title":"Mechanisms of bone development and repair","volume":"21","author":"Salhotra","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1210\/er.2017-00064","article-title":"Energy Metabolism of the Osteoblast: Implications for Osteoporosis","volume":"38","author":"Lee","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kito, H., and Ohya, S. (2021). Role of K+ and Ca2+-Permeable Channels in Osteoblast Functions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910459"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Makino, T., Tsukazaki, H., Ukon, Y., Tateiwa, D., Yoshikawa, H., and Kaito, T. (2018). The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082430"},{"key":"ref_47","unstructured":"Henry, J.P., and Bordoni, B. (2024). Histology, Osteoblasts. StatPearls, StatPearls Publishing."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/jbmr.3332","article-title":"Osteoblast-Derived Extracellular Vesicles Are Biological Tools for the Delivery of Active Molecules to Bone","volume":"33","author":"Cappariello","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/1873-3468.12024","article-title":"Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression","volume":"590","author":"Cui","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41586-018-0482-7","article-title":"Coupling of bone resorption and formation by RANKL reverse signalling","volume":"561","author":"Ikebuchi","year":"2018","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1478-811X-12-26","article-title":"Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential","volume":"12","author":"Lopatina","year":"2014","journal-title":"Cell Commun. Signal"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s00109-013-1110-5","article-title":"Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model","volume":"92","author":"Bian","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1089\/scd.2012.0095","article-title":"Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo","volume":"21","author":"Zhang","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e12570","DOI":"10.1111\/cpr.12570","article-title":"Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1\u03b1-mediated promotion of angiogenesis in a rat model of stabilized fracture","volume":"52","author":"Zhang","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"30081","DOI":"10.1021\/acsami.8b08449","article-title":"Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment","volume":"10","author":"Zhang","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1002\/stem.2618","article-title":"Hypoxia Inducible Factor-1\u03b1 Potentiates Jagged 1-Mediated Angiogenesis by Mesenchymal Stem Cell-Derived Exosomes","volume":"35","author":"Ciria","year":"2017","journal-title":"Stem Cells"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Xie, H., Wang, Z., Zhang, L., Lei, Q., Zhao, A., Wang, H., Li, Q., Cao, Y., Jie Zhang, W., and Chen, Z. (2017). Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities. Sci. Rep., 7.","DOI":"10.1038\/srep45622"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1172\/JCI12037","article-title":"Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis","volume":"107","author":"Nakajima","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.bone.2008.06.019","article-title":"Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model","volume":"43","author":"Patel","year":"2008","journal-title":"Bone"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lee, Y.-H., Park, H.-K., Auh, Q.-S., Nah, H., Lee, J.S., Moon, H.-J., Heo, D.N., Kim, I.S., and Kwon, I.K. (2020). Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041541"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/s13287-018-1047-2","article-title":"Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells","volume":"9","author":"Chen","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1302\/2046-3758.74.BJR-2018-0006","article-title":"Harnessing extracellular vesicles to direct endochondral repair of large bone defects","volume":"7","author":"Ferreira","year":"2018","journal-title":"Bone Joint Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1007\/s00198-009-0925-y","article-title":"Osteoporosis in china","volume":"20","author":"Wang","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"(2001). NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7-29, 2000: Highlights of the conference. South. Med. J., 94, 569\u2013573.","DOI":"10.1097\/00007611-200194060-00004"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1016\/j.ajpath.2011.07.015","article-title":"Protease-activated receptor 1 and hematopoietic cell tissue factor are required for hepatic steatosis in mice fed a Western diet","volume":"179","author":"Kassel","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMcp1513724","article-title":"Clinical Practice. Postmenopausal Osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"He, X.-Y., Yu, H.-M., Lin, S., and Li, Y.-Z. (2021). Advances in the application of mesenchymal stem cells, exosomes, biomimetic materials, and 3D printing in osteoporosis treatment. Cell Mol. Biol. Lett., 26.","DOI":"10.1186\/s11658-021-00291-8"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8777","DOI":"10.18632\/aging.102264","article-title":"LncRNA MALAT1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microRNA-34c\/SATB2 axis","volume":"11","author":"Yang","year":"2019","journal-title":"Aging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jbiosc.2021.02.007","article-title":"Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts","volume":"131","author":"Zhang","year":"2021","journal-title":"J. Biosci. Bioeng."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1002\/cbin.11690","article-title":"M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98\/DUSP1\/JNK axis","volume":"45","author":"Yu","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1002\/jcp.30331","article-title":"Exosomes derived from vascular endothelial cells antagonize glucocorticoid-induced osteoporosis by inhibiting ferritinophagy with resultant limited ferroptosis of osteoblasts","volume":"236","author":"Yang","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41413-023-00313-5","article-title":"The role and applications of extracellular vesicles in osteoporosis","volume":"12","author":"Fang","year":"2024","journal-title":"Bone Res."},{"key":"ref_73","unstructured":"(2018). GBD 2017 Risk Factor Collaborators Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392, 1923\u20131994."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"Barr","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/annrheumdis-2012-202453","article-title":"Strontium ranelate: Ready for clinical use as disease-modifying osteoarthritis drug?","volume":"72","author":"Lafeber","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/s11926-013-0328-0","article-title":"Osteoarthritis and osteoporosis: What is the overlap?","volume":"15","author":"Bultink","year":"2013","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cosenza, S., Ruiz, M., Toupet, K., Jorgensen, C., and No\u00ebl, D. (2017). Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-15376-8"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.2217\/nnm-2018-0498","article-title":"Primary chondrocyte exosomes mediate osteoarthritis progression by regulating mitochondrion and immune reactivity","volume":"14","author":"Zheng","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41536-022-00250-7","article-title":"Chondrogenic primed extracellular vesicles activate miR-455\/SOX11\/FOXO axis for cartilage regeneration and osteoarthritis treatment","volume":"7","author":"Sun","year":"2022","journal-title":"NPJ Regen. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biomaterials.2019.02.006","article-title":"MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis","volume":"200","author":"Zhang","year":"2019","journal-title":"Biomaterials"},{"key":"ref_81","first-page":"423","article-title":"Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis","volume":"22","author":"Liu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"573528","DOI":"10.1155\/2012\/573528","article-title":"Immunosuppressive exosomes: A new approach for treating arthritis","volume":"2012","author":"Yang","year":"2012","journal-title":"Int. J. Rheumatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41419-021-03430-3","article-title":"Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery","volume":"12","author":"Hu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s13577-023-00881-y","article-title":"Bone marrow mesenchymal stem cells derived exosomal Lnc TUG1 promotes bone fracture recovery via miR-22-5p\/Anxa8 axis","volume":"36","author":"Li","year":"2023","journal-title":"Hum. Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13287-020-1562-9","article-title":"Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion","volume":"11","author":"Zhang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.actbio.2019.12.020","article-title":"Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126","volume":"103","author":"Liu","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Huber, J., Longaker, M.T., and Quarto, N. (2023). Circulating and extracellular vesicle-derived microRNAs as biomarkers in bone-related diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1168898"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"16015","DOI":"10.1038\/celldisc.2016.15","article-title":"Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity","volume":"2","author":"Sun","year":"2016","journal-title":"Cell Discov."},{"key":"ref_89","first-page":"1921","article-title":"Identification of key microRNAs and target genes for the diagnosis of bone nonunion","volume":"21","author":"Xiong","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1007\/s00264-018-4093-6","article-title":"Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis","volume":"42","author":"Zhao","year":"2018","journal-title":"Int. Orthop."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1759720X221082917","DOI":"10.1177\/1759720X221082917","article-title":"Circulating microRNAs differentiate fast-progressing from slow-progressing and non-progressing knee osteoarthritis in the Osteoarthritis Initiative cohort","volume":"14","author":"Ali","year":"2022","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1002\/jbmr.3976","article-title":"The miR-143\/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1","volume":"35","author":"Urdinez","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Raimondo, S., Urz\u00ec, O., Conigliaro, A., Bosco, G.L., Parisi, S., Carlisi, M., Siragusa, S., Raimondi, L., Luca, A.D., and Giavaresi, G. (2020). Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma. Cancers, 12.","DOI":"10.3390\/cancers12020449"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"109935","DOI":"10.1016\/j.cellsig.2021.109935","article-title":"Osteosarcoma-derived exosomal miR-501-3p promotes osteoclastogenesis and aggravates bone loss","volume":"82","author":"Lin","year":"2021","journal-title":"Cell Signal"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Man, K., Brunet, M.Y., Jones, M.-C., and Cox, S.C. (2020). Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications. Nanomaterials, 10.","DOI":"10.3390\/nano10091838"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Lu, M., and Huang, Y. (2020). Bioinspired exosome-like therapeutics and delivery nanoplatforms. Biomaterials, 242.","DOI":"10.1016\/j.biomaterials.2020.119925"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Pizzicannella, J., Gugliandolo, A., Orsini, T., Fontana, A., Ventrella, A., Mazzon, E., Bramanti, P., Diomede, F., and Trubiani, O. (2019). Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF\/VEGFR2 Expression During Bone Regeneration. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00512"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Pizzicannella, J., Diomede, F., Gugliandolo, A., Chiricosta, L., Bramanti, P., Merciaro, I., Orsini, T., Mazzon, E., and Trubiani, O. (2019). 3D Printing PLA\/Gingival Stem Cells\/ EVs Upregulate miR-2861 and -210 during Osteoangiogenesis Commitment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133256"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1089\/ten.tea.2020.0141","article-title":"Bone Marrow Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Periodontal Regeneration","volume":"27","author":"Liu","year":"2021","journal-title":"Tissue Eng. Part. A"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1021\/acs.nanolett.9b00287","article-title":"Reversal of Osteoporotic Activity by Endothelial Cell-Secreted Bone Targeting and Biocompatible Exosomes","volume":"19","author":"Song","year":"2019","journal-title":"Nano Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4726","DOI":"10.1021\/acs.jafc.3c07095","article-title":"Oral Milk-Derived Extracellular Vesicles Inhibit Osteoclastogenesis and Ameliorate Bone Loss in Ovariectomized Mice by Improving Gut Microbiota","volume":"72","author":"Hao","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1002\/jcb.25225","article-title":"The Role of MicroRNA, miR-24, and Its Target CHI3L1 in Osteomyelitis Caused by Staphylococcus aureus","volume":"116","author":"Jin","year":"2015","journal-title":"J. Cell Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7150\/thno.21945","article-title":"Exosome Theranostics: Biology and Translational Medicine","volume":"8","author":"He","year":"2018","journal-title":"Theranostics"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jconrel.2014.12.013","article-title":"Biodistribution and delivery efficiency of unmodified tumor-derived exosomes","volume":"199","author":"Smyth","year":"2015","journal-title":"J. Control Release"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13287-023-03275-x","article-title":"Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration","volume":"14","author":"Lu","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7150\/ijbs.14809","article-title":"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","volume":"12","author":"Qi","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.actbio.2019.01.006","article-title":"Exosome-integrated titanium oxide nanotubes for targeted bone regeneration","volume":"86","author":"Wei","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"27486","DOI":"10.1021\/acsami.3c00898","article-title":"Engineering 3D-Printed Strontium-Titanium Scaffold-Integrated Highly Bioactive Serum Exosomes for Critical Bone Defects by Osteogenesis and Angiogenesis","volume":"15","author":"Liu","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e12160","DOI":"10.1002\/jev2.12160","article-title":"Reversing the surface charge of MSC-derived small extracellular vesicles by \u03b5PL-PEG-DSPE for enhanced osteoarthritis treatment","volume":"10","author":"Feng","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/9\/548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:09Z","timestamp":1760110929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/9\/548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":110,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cimb46090548"],"URL":"https:\/\/doi.org\/10.3390\/cimb46090548","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,23]]}}}