{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:00Z","timestamp":1792789620362,"version":"4.5.0"},"reference-count":72,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["2023R1A2C3003807"],"award-info":[{"award-number":["2023R1A2C3003807"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["2022R1I1A1A01068486"],"award-info":[{"award-number":["2022R1I1A1A01068486"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["23A0206L1"],"award-info":[{"award-number":["23A0206L1"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2023R1A2C3003807"],"award-info":[{"award-number":["2023R1A2C3003807"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2022R1I1A1A01068486"],"award-info":[{"award-number":["2022R1I1A1A01068486"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["23A0206L1"],"award-info":[{"award-number":["23A0206L1"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Fund for Regenerative Medicine (KFRM)","award":["2023R1A2C3003807"],"award-info":[{"award-number":["2023R1A2C3003807"]}]},{"name":"Korean Fund for Regenerative Medicine (KFRM)","award":["2022R1I1A1A01068486"],"award-info":[{"award-number":["2022R1I1A1A01068486"]}]},{"name":"Korean Fund for Regenerative Medicine (KFRM)","award":["23A0206L1"],"award-info":[{"award-number":["23A0206L1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.<\/jats:p>","DOI":"10.3390\/ijms25105242","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:03:08Z","timestamp":1715673788000},"page":"5242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-6623","authenticated-orcid":false,"given":"Jun Yong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"},{"name":"Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si 16419, Republic of Korea"},{"name":"Intelligent Precision of Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Gyu","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Min","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-6165","authenticated-orcid":false,"given":"Duck Hyun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hyuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"ATEMs, Jeongui-ro 8-gil, Songpa-gu, Seoul-si 05836, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungsoo","family":"Rho","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8926-3418","authenticated-orcid":false,"given":"Chun Gwon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si 16419, Republic of Korea"},{"name":"Intelligent Precision of Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-1672","authenticated-orcid":false,"given":"Won-Kyu","family":"Rhim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"},{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-7883","authenticated-orcid":false,"given":"Dong Keun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41467-017-01868-8","article-title":"Estrogen-Related Receptor \u03b3 Causes Osteoarthritis by Upregulating Extracellular Matrix-Degrading Enzymes","volume":"8","author":"Son","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/s41551-021-00780-3","article-title":"Amelioration of Post-Traumatic Osteoarthritis via Nanoparticle Depots Delivering Small Interfering RNA to Damaged Cartilage","volume":"5","author":"Bedingfield","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_4","first-page":"349","article-title":"Is a Combination of Exercise and Dry Needling Effective for Knee OA?","volume":"21","year":"2020","journal-title":"Pain Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Romero, E.A.S., Gonz\u00e1lez-Zamorano, Y., Arribas-Romano, A., Mart\u00ednez-Pozas, O., Espinar, E.F., Pedersini, P., Villafa\u00f1e, J.H., P\u00e9rez, J.L.A., and Fern\u00e1ndez-Carnero, J. (2021). Efficacy of Manual Therapy on Facilitatory Nociception and Endogenous Pain Modulation in Older Adults with Knee Osteoarthritis: A Case Series. Appl. Sci., 11.","DOI":"10.3390\/app11041895"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sinatti, P., S\u00e1nchez Romero, E.A., Mart\u00ednez-Pozas, O., and Villafa\u00f1e, J.H. (2022). Effects of Patient Education on Pain and Function and Its Impact on Conservative Treatment in Elderly Patients with Pain Related to Hip and Knee Osteoarthritis: A Systematic Review. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19106194"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/TGR.0000000000000337","article-title":"Impact on Blood Tests of Lower Limb Joint Replacement for the Treatment of Osteoarthritis","volume":"37","author":"Battaglino","year":"2021","journal-title":"Top. Geriatr. Rehabil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1148\/radiol.2020200771","article-title":"Intra-Articular Corticosteroid Injections for the Treatment of Hip and Knee Osteoarthritis-Related Pain: Considerations and Controversies with a Focus on Imaging-Radiology Scientific Expert Panel","volume":"297","author":"Guermazi","year":"2020","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kim, J.G., Kim, K.-I., Park, K.B., Park, Y.G., Bae, J.H., Seo, Y.J., Seon, J.K., Shon, O.J., Ahn, J.H., and Wang, L. (2023). Safety and Effectiveness of Intra-Articular Injection of a Highly Cross-Linked Hyaluronic Acid, LBSA0103 (Synovian): Results from a Post-Marketing Surveillance Study in South Korea. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0287222"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9419","DOI":"10.1038\/s41598-023-35982-z","article-title":"A Randomized Controlled Trial for Comparing Efficacy and Safety between Intraarticular Polynucleotide and Hyaluronic Acid for Knee Osteoarthritis Treatment","volume":"13","author":"Kim","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Kim, Y.N., Lee, Y.J., Sim, S.E., Ko, Y.R., Shim, J.W., Lee, K.S., Joo, M., and Park, H.J. (2021). Pilot Study to Evaluate the Efficacy of Polynucleotide Sodium Compared to Sodium Hyaluronate and Crosslinked Sodium Hyaluronate in Patients with Knee Osteoarthritis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10051138"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314231164765","article-title":"Regeneration of Articular Cartilage Defects: Therapeutic Strategies and Perspectives","volume":"14","author":"Guo","year":"2023","journal-title":"J. Tissue Eng."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lee, H.-I., Rhim, W.K., Kang, E.Y., Choi, B., Kim, J.H., and Han, D.K. (2021). A Multilayer Functionalized Drug-Eluting Balloon for Treatment of Coronary Artery Disease. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050614"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1039\/D2BM01673G","article-title":"Endogenous Stimulus-Responsive Nitric Oxide Releasing Bioactive Liposome for a Multilayered Drug-Eluting Balloon","volume":"11","author":"Seo","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314221132093","article-title":"A New Cell-Free Therapeutic Strategy for Liver Regeneration: Human Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles","volume":"13","author":"Li","year":"2022","journal-title":"J. Tissue Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314231196275","article-title":"Tendon Tissue Engineering: An Overview of Biologics to Promote Tendon Healing and Repair","volume":"14","author":"Citro","year":"2023","journal-title":"J. Tissue Eng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s13770-023-00579-0","article-title":"Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the MiR-181a-5p\/Smad2 Axis","volume":"21","author":"Shao","year":"2023","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-022-00359-3","article-title":"Extracellular Vesicles through the Blood\u2013Brain Barrier: A Review","volume":"19","author":"Polakovicova","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Koh, H.B., Kim, H.J., Kang, S.W., and Yoo, T.H. (2023). Exosome-Based Drug Delivery: Translation from Bench to Clinic. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15082042"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40478-024-01777-0","article-title":"Extracellular Vesicle Encapsulated Nicotinamide Delivered via A Trans-Scleral Route Provides Retinal Ganglion Cell Neuroprotection","volume":"12","author":"Kim","year":"2024","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_21","first-page":"169","article-title":"Dual-Engineered Cartilage-Targeting Extracellular Vesicles Derived from Mesenchymal Stem Cells Enhance Osteoarthritis Treatment via MiR-223\/NLRP3\/Pyroptosis Axis: Toward a Precision Therapy","volume":"30","author":"Liu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.7150\/thno.69368","article-title":"Chondrocyte-Specific Genomic Editing Enabled by Hybrid Exosomes for Osteoarthritis Treatment","volume":"12","author":"Liang","year":"2022","journal-title":"Theranostics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314231185848","article-title":"New Insights into Balancing Wound Healing and Scarless Skin Repair","volume":"14","author":"Zhou","year":"2023","journal-title":"J. Tissue Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.1039\/D2BM01478E","article-title":"Erythrocyte Membrane Camouflaged SiRNA\/Chemodrug Nanoassemblies for Cancer Combination Therapy","volume":"10","author":"Xu","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1124\/dmd.121.000381","article-title":"Nonclinical Pharmacokinetics and Absorption, Distribution, Metabolism, and Excretion of Givosiran, the First Approved n-Acetylgalactosamine-Conjugated Rna Interference Therapeutic","volume":"49","author":"Li","year":"2021","journal-title":"Drug Metab. Dispos."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rhim, W.K., Kim, J.Y., Lee, S.Y., Cha, S.G., Park, J.M., Park, H.J., Park, C.G., and Han, D.K. (2023). Recent Advances in Extracellular Vesicle Engineering and Its Applications to Regenerative Medicine. Biomater. Res., 27.","DOI":"10.1186\/s40824-023-00468-6"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s12015-017-9760-2","article-title":"Gene Delivery Approaches for Mesenchymal Stem Cell Therapy: Strategies to Increase Efficiency and Specificity","volume":"13","author":"Oggu","year":"2017","journal-title":"Stem Cell Rev. Reports"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1089\/ten.tec.2009.0806","article-title":"Binding and Release Characteristics of Insulin-like Growth Factor-1 from a Collagen-Glycosaminoglycan Scaffold","volume":"16","author":"Mullen","year":"2010","journal-title":"Tissue Eng.\u2014Part C Methods"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhong, J., Zhang, J., Zhou, Z., Pan, D., Zhao, D., Dong, H., and Yao, B. (2023). Novel Insights into the Effect of Deer IGF-1 on Chondrocyte Viability and IL-1\u03b2-Induced Inflammation Response. J. Biochem. Mol. Toxicol., 37.","DOI":"10.1002\/jbt.23227"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40580-022-00349-z","article-title":"Bolstering the Secretion and Bioactivities of Umbilical Cord MSC-Derived Extracellular Vesicles with 3D Culture and Priming in Chemically Defined Media","volume":"9","author":"Kim","year":"2022","journal-title":"Nano Converg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314211008626","article-title":"Defined MSC Exosome with High Yield and Purity to Improve Regenerative Activity","volume":"12","author":"Kim","year":"2021","journal-title":"J. Tissue Eng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s13770-021-00352-1","article-title":"Comparative Analysis of MSC-Derived Exosomes Depending on Cell Culture Media for Regenerative Bioactivity","volume":"18","author":"Kim","year":"2021","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kim, J.Y., Rhim, W., Woo, J., Cha, S., Park, C.G., and Han, D.K. (2022). The Upregulation of Regenerative Activity for Extracellular Vesicles with Melatonin Modulation in Chemically Defined Media. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315089"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal Information for Studies of Extracellular Vesicles (MISEV2023): From Basic to Advanced Approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1002\/art.38799","article-title":"Dkk-1-Mediated Inhibition of Wnt Signaling in Bone Ameliorates Osteoarthritis in Mice","volume":"66","author":"Bouaziz","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_36","first-page":"1","article-title":"Hepatocyte Growth Factor in Normal and Diseased Bone and Joint Tissues","volume":"2","author":"Adamopoulos","year":"2006","journal-title":"Curr. Rheumatol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.3389\/fimmu.2017.01638","article-title":"Thrombospondin-1 Partly Mediates the Cartilage Protective Effect of Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis","volume":"8","author":"Maumus","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8060","DOI":"10.1002\/jcp.30494","article-title":"DPP4 Reduces Proinflammatory Cytokine Production in Human Rheumatoid Arthritis Synovial Fibroblasts","volume":"236","author":"Han","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/CJP.CJP_11_19","article-title":"Fibroblast Growth Factors: Potential Novel Targets for Regenerative Therapy of Osteoarthritis","volume":"62","author":"Chen","year":"2019","journal-title":"Chin. J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3889\/oamjms.2022.10679","article-title":"Biological Therapy for Osteoarthritis, Efficacy and Safety: Focus on Monoclonal Antibodies against Nerve Growth Factor and Fibroblast Growth Factor-18","volume":"10","author":"Zaripova","year":"2022","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.37796\/2211-8039.1308","article-title":"Fibroblast Growth Factor Receptor 1-Bound Extracellular Vesicle as Novel Therapy for Osteoarthritis","volume":"12","author":"Nolan","year":"2022","journal-title":"Biomed."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S454","DOI":"10.1016\/j.joca.2016.01.829","article-title":"Expression of GM-CSF and Its Receptor CD116 in the Synovium of OA Patients Is Negatively Correlated with Pain","volume":"24","author":"Pustjens","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.4049\/jimmunol.1800665","article-title":"CSF-1 in Inflammatory and Arthritic Pain Development","volume":"201","author":"Saleh","year":"2018","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13075-021-02442-w","article-title":"Macrophage Migration Inhibitory Factor May Play a Protective Role in Osteoarthritis","volume":"23","author":"Liu","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"117487","DOI":"10.1016\/j.cca.2023.117487","article-title":"ICAM-1 and VCAM-1: Gatekeepers in Various Inflammatory and Cardiovascular Disorders","volume":"548","author":"Singh","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_47","first-page":"138","article-title":"New Insights into Growth Hormone Receptor Function and Clinical Implications","volume":"69","author":"Lichanska","year":"2008","journal-title":"Horm. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v18.i1.10","article-title":"Ligand-Receptor-Mediated Drug Delivery: An Emerging Paradigm in Cellular Drug Targeting","volume":"18","author":"Vyas","year":"2001","journal-title":"Crit. Rev. Ther. Drug Carr. Syst."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chulpanova, D.S., Kitaeva, K.V., Green, A.R., Rizvanov, A.A., and Solovyeva, V.V. (2020). Molecular Aspects and Future Perspectives of Cytokine-Based Anti-Cancer Immunotherapy. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00402"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nri1688","article-title":"Interleukin-21: A Modulator of Lymphoid Proliferation, Apoptosis and Differentiation","volume":"5","author":"Leonard","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Coleman, W.B., and Tsongalis, G.J. (2016). The Molecular Basis of Human Cancer, Humana Press.","DOI":"10.1007\/978-1-59745-458-2"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.24843\/ESTL.2021.v19.i02.p01","article-title":"Terapi Mesenchymal Stem Cell Sebagai Modalitas Tatalaksana Osteoartritis","volume":"19","author":"Theodorus","year":"2022","journal-title":"Essent. Essence Sci. Med. J."},{"key":"ref_53","first-page":"1","article-title":"Multiplexed PLGA Scaffolds with Nitric Oxide-Releasing Zinc Oxide and Melatonin-Modulated Extracellular Vesicles for Severe Chronic Kidney Disease","volume":"59","author":"Rhim","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cha, S.G., Rhim, W.K., Kim, J.Y., Lee, E.H., Lee, S.Y., Park, J.M., Lee, J.E., Yoon, H., Park, C.G., and Kim, B.S. (2023). Kidney Tissue Regeneration Using Bioactive Scaffolds Incorporated with Differentiating Extracellular Vesicles and Intermediate Mesoderm Cells. Biomater. Res., 27.","DOI":"10.1186\/s40824-023-00471-x"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/acssensors.0c02519","article-title":"Real-Time Evaluation of Hydrogen Peroxide Injuries in Pulmonary Fibrosis Mice Models with a Mitochondria-Targeted Near-Infrared Fluorescent Probe","volume":"6","author":"Song","year":"2021","journal-title":"ACS Sensors"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbcan.2006.02.001","article-title":"Pro-Apoptotic Role of NF-\u039aB: Implications for Cancer Therapy","volume":"1766","author":"Radhakrishnan","year":"2006","journal-title":"Biochim. Biophys. Acta\u2014Rev. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s13770-021-00406-4","article-title":"Secretome of Stem Cells: Roles of Extracellular Vesicles in Diseases, Stemness, Differentiation, and Reprogramming","volume":"19","author":"Kim","year":"2022","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S1357-4310(97)01128-3","article-title":"Cell Adhesion: A New Target for Therapy","volume":"3","author":"Buckley","year":"1997","journal-title":"Mol. Med. Today"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Miao, S., Zhou, J., Liu, B., Lei, X., Wang, T., Hao, X., Cheng, P., Wu, H., Song, Y., and Pei, G. (2022). A 3D Bioprinted Nano-Laponite Hydrogel Construct Promotes Osteogenesis by Activating PI3K\/AKT Signaling Pathway. Mater. Today Bio, 16.","DOI":"10.1016\/j.mtbio.2022.100342"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.ceb.2009.06.004","article-title":"Control of Cell Adhesion Dynamics by Rap1 Signaling","volume":"21","author":"Boettner","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ydbio.2006.06.045","article-title":"Ras Signaling Is Essential for Lens Cell Proliferation and Lens Growth during Development","volume":"298","author":"Xie","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/gt.2009.66","article-title":"Therapeutic Silencing of an Endogenous Gene by SiRNA Cream in an Arthritis Model Mouse","volume":"16","author":"Takanashi","year":"2009","journal-title":"Gene Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","article-title":"Therapeutic siRNA: State of the Art","volume":"5","author":"Hu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"31","DOI":"10.9734\/jamps\/2023\/v25i1596","article-title":"SiRNA: A Comprehensive Review of Marketed Products till August 2022","volume":"25","author":"Ghosh","year":"2023","journal-title":"J. Adv. Med. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7139","DOI":"10.1038\/s41467-022-34830-4","article-title":"Cholesterol-Induced LRP3 Downregulation Promotes Cartilage Degeneration in Osteoarthritis by Targeting Syndecan-4","volume":"13","author":"Cao","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1093\/ndt\/gfad063c_3633","article-title":"Direct exosome transfection with fluorescently labeled small rnas is a useful tool for exosomal cargo trafficking and rnai in cultured podocytes","volume":"38","author":"Lange","year":"2023","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eaat8800","DOI":"10.1126\/scitranslmed.aat8800","article-title":"Cartilage-Penetrating Nanocarriers Improve Delivery and Efficacy of Growth Factor Treatment of Osteoarthritis","volume":"10","author":"Geiger","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.actbio.2022.08.010","article-title":"Charge-Based Drug Delivery to Cartilage: Hydrophobic and Not Electrostatic Interactions Are the Dominant Cause of Competitive Binding of Cationic Carriers in Synovial Fluid","volume":"151","author":"Vedadghavami","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jconrel.2013.04.022","article-title":"Functionalized Nanoparticles Provide Early Cardioprotection after Acute Myocardial Infarction","volume":"170","author":"Chang","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10","DOI":"10.22456\/1679-9216.87212","article-title":"Autogenous Osteochondral Graft Associated with IGF-1 in Induced Articular Cartilage Lesion in Rabbits [Enxerto Osteocondral Aut\u00f3geno Associado Ao IGF-1 Em Les\u00e3o Induzida Na Cartilagem Articular de Coelhos]","volume":"46","author":"Kawamoto","year":"2018","journal-title":"Acta Sci. Vet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1177\/44.2.8609369","article-title":"Insulin-like Growth Factor (IGF) Receptor, IGF-I, Interleukin-1\u03b2 (IL-1\u03b2), and IL-6 MRNA Expression in Osteoarthritic and Normal Human Cartilage","volume":"44","author":"Middleton","year":"1996","journal-title":"J. Histochem. Cytochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"14475","DOI":"10.1021\/acsnano.1c04005","article-title":"Top-Down Fabricated MicroPlates for Prolonged, Intra-Articular Matrix Metalloproteinase 13 SiRNA Nanocarrier Delivery to Reduce Post-Traumatic Osteoarthritis","volume":"15","author":"Bedingfield","year":"2021","journal-title":"ACS Nano"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5242\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:21Z","timestamp":1760107461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,11]]},"references-count":72,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105242"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105242","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,11]]}}}