外泌体在骨关节炎诊断和治疗中的现状、机遇与挑战

doi:10.3969/j.issn.1006-5725.2026.16.009

摘要/Abstract

摘要：

骨关节炎是一种常见的关节退行性疾病，严重影响患者生活质量。外泌体作为细胞间通讯的重要媒介，因其独特的生物学特性，在骨关节炎的诊断和治疗中展现出巨大潜力。该文综述了外泌体的结构与组成，探讨了其作为骨关节炎诊断生物标志物的可能性，分析了外泌体在骨关节炎治疗中的价值，并讨论了当前面临的挑战与未来展望，旨在为外泌体在骨关节炎领域的进一步研究和应用提供参考。

关键词: 骨关节炎, 外泌体, 诊断, 治疗

Abstract:

Osteoarthritis （OA） is a highly prevalent degenerative joint disease that substantially impairs patients' quality of life. As key mediators of intercellular communication， exosomes have emerged as promising candidates for the diagnosis and therapeutic management of OA owing to their unique biological characteristics. This review summarizes the structural architecture and molecular composition of exosomes， appraises their potential as diagnostic biomarkers for OA， and discusses their translational therapeutic value. We also delineate the current challenges encountered in clinical translation and outline future research directions， with the aim of providing a robust reference for advancing further investigation and clinical translation of exosome-based strategies in the OA research field.

Key words: osteoarthritis, exosomes, diagnosis, treatment

中图分类号:

R684.3

张晓非, 徐康, 孙逊. 外泌体在骨关节炎诊断和治疗中的现状、机遇与挑战[J]. 实用医学杂志, 2026, 42(16): 2937-2944.

Xiaofei Zhang, Kang Xu, Xun Sun. The current status， opportunities and challenges of exosomes in the diagnosis and treatment of osteoarthritis[J]. The Journal of Practical Medicine, 2026, 42(16): 2937-2944.

参考文献 69

[1]	Long huibin， Liu Qiong， Yin Heyong， et al. Prevalence trends of site-specific osteoarthritis from 1990 to 2019： Findings from the global burden of disease study 2019［J］. Arthritis Rheumatol， 2022， 74（7）： 1172-1183. doi：10.1002/art.42089 .
[2]	Steinmetz J D， Culbreth G T， Haile L M， et al. Global， regional， and national burden of osteoarthritis， 1990–2020 and projections to 2050： A systematic analysis for the Global Burden of Disease Study 2021［J］. Lancet Rheumatol， 2023， 5（9）： e508-e522. doi：10.1016/s2665-9913（23）00163-7 .
[3]	Syed N H， Misbah I， Azlan M， et al. Exosomes in osteoarthritis： A review on their isolation techniques and therapeutic potential［J］. Indian J Orthop， 2024， 58（7）： 866-875. doi：10.1007/s43465-024-01175-7 .
[4]	Okuyan H M， Coşkun A， Begen M A. Current status， opportunities， and challenges of exosomes in diagnosis and treatment of osteoarthritis［J］. Life Sci， 2025， 362： 123365. doi：10.1016/j.lfs.2024.123365 .
[5]	中国骨关节炎诊疗指南专家组，中国老年保健协会疼痛病学分会，黄东，等. 中国骨关节炎诊疗指南（2024版）［J］. 中华疼痛学杂志， 2024， 20（3）： 323-338. doi：10.3760/cma.j.cn101658-20240618-00074 .
[6]	Xiang Wei， Zheng Qianghua， Liu Anming， et al. Recent therapeutic strategies for excessive chondrocyte death in osteoarthritis： A review［J］. Orthop Surg， 2023， 15（6）： 1437-1453. doi：10.1111/os. 13718 .
[7]	曹力. 人工关节置换术后假体周围感染治疗中抗生素的应用［J］. 中华骨与关节外科杂志， 2024， 17（11）： 961-967. doi：10.3969/j.issn.2095-9958.2024.11.01 .
[8]	欧光林，刘运忠，谢明冬，等. 人工关节置换术后肺栓塞治疗的对照研究［J］. 中国防痨杂志， 2024， 46（S2）： 245-246.
[9]	林才渊，李志鹏，张志广，等. 加速康复下肢关节置换深静脉血栓形成的相关因素［J］. 中国矫形外科杂志， 2024， 32（7）： 591-595. doi：10.3977/j.issn.1005-8478.2024.07.03 .
[10]	Dimik M， Abeysinghe P， Logan J， et al. The exosome： A review of current therapeutic roles and capabilities in human reproduction［J］. Drug Deliv Transl Res， 2023， 13（2）： 473-502. doi：10.1007/s13346-022-01225-3 .
[11]	Xiong Min， Chen Zhen， Tian Jiaqi， et al. Exosomes derived from programmed cell death： Mechanism and biological significance［J］. Cell Commun Signal， 2024， 22（1）： 156. doi：10.1186/s12964-024-01521-0 .
[12]	Krylova S V， Feng D. The machinery of exosomes： Biogenesis， release， and uptake［J］. Int J Mol Sci， 2023， 24（2）： 1337. doi：10.3390/ijms24021337 .
[13]	Kalluri R， Lebleu V S. The biology， function， and biomedical applications of exosomes［J］. Science， 2020， 367（6478）： eaau6977. doi：10.1126/science.aau6977 .
[14]	Cunha E Rocha K， Ying W， Olefsky J M. Exosome-mediated impact on systemic metabolism［J］. Annu Rev Physiol， 2024， 86： 225-253. doi：10.1146/annurev-physiol-042222-024535 .
[15]	Lai J J， Chau Z L， Chen S Y， et al. Exosome processing and characterization approaches for research and technology development［J］. Adv Sci， 2022， 9（15）： 2103222. doi：10.1002/advs. 202103222 .
[16]	Yang Yihui， Yu Zhujun， Dou Wei， et al. The biology， function， and applications of exosomes as novel biomarkers for in-vivo drug exposure variability［J］. Front Pharmacol， 2026， 17： 1822691. doi：10.3389/fphar.2026.1822691 .
[17]	Yadav S， Maity P， Kapat K. The opportunities and challenges of mesenchymal stem cells-derived exosomes in theranostics and regenerative medicine［J］. Cells， 2024， 13（23）： 1956. doi：10.3390/cells13231956 .
[18]	Cueva J H， Castillo D， Espinós-Morató H， et al. Detection and classification of knee osteoarthritis［J］. Diagnostics， 2022， 12（10）： 2362. doi：10.3390/diagnostics12102362 .
[19]	Shinde M， Pardeshi D， Patel M， et al. Grading of knee osteoarthritis based on kellgren-Lawrence classification and finding an association between radiographic features and pain： A cross-sectional study at a tertiary health care hospital［J］. Cureus， 2024， 16（11）： e73224. doi：10.7759/cureus.73224 .
[20]	Shin D， Choi J H， Jeon M J， et al. Synovial exosomal type II collagen as a biomarker for osteoarthritis Progression： From molecular evaluation to AI-powered SERS-based diagnosis［J］. Biosens Bioelectron， 2026， 293： 118180. doi：10.1016/j.bios.2025. 118180 .
[21]	Zhao Ye， Xu Juan. Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis［J］. Int Orthop， 2018， 42（12）： 2865-2872. doi：10.1007/s00264-018-4093-6 .
[22]	Kang Y， Song J， Kim D， et al. PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770［J］. J Orthop Res， 2016， 34（3）： 412-418. doi：10.1002/jor.23046 .
[23]	Kolhe R， Owens V， Sharma A， et al. Sex-specific differences in extracellular vesicle protein cargo in synovial fluid of patients with osteoarthritis［J］. Life （Basel）， 2020， 10（12）： 337. doi：10.3390/life10120337 .
[24]	Veronesi F， Salamanna F， Sacchi G， et al. Circulating biomarkers in osteoarthritis： A systematic review unveiling key trends and future prospects［J］. Pathol Res Pract， 2025， 276： 156281. doi：10.1016/j.prp.2025.156281 .
[25]	Zeng Guangxuan， Deng Gang， Xiao Shiliang， et al. Fibroblast-like synoviocytes-derived exosomal PCGEM1 accelerates IL-1β-induced apoptosis and cartilage matrix degradation by miR-142-5p/RUNX2 in chondrocytes［J］. Immunol Invest， 2022， 51（5）： 1284-1301. doi：10.1080/08820139.2021.1936010 .
[26]	Brenis Gómez C M， Plasencia-Rodríguez C， Novella-Navarro M， et al. Exosomal protein biomarkers in arthritis： Deciphering the inflammatory profiles of RA and OA［J］. Biomedicines， 2025， 13（6）： 1283. doi：10.3390/biomedicines13061283 .
[27]	Ren Xiaojun， Zhang Manling， Shi Zhaohong， et al. Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in Crohn′s disease by integrating bioinformatics and machine learning［J］. Autoimmunity， 2024， 57（1）： 2422352. doi：10.1080/08916934.2024.2422352 .
[28]	Yang Xiaohe， Chen Shuyin， Zhou Quanfa， et al. Exosomes in osteoarthritis： Breakthrough innovations and advanced tissue engineering for cartilage regeneration since 2020［J］. Biomedicines， 2025， 13（10）： 2486. doi：10.3390/biomedicines13102486 .
[29]	D′Arrigo D， Salerno M， De Marziani L， et al. A call for standardization for secretome and extracellular vesicles in osteoarthritis： Results show disease-modifying potential， but protocols are too heterogeneous—a systematic review［J］. Hum Cell， 2024， 37（5）： 1243-1275. doi：10.1007/s13577-024-01084-9 .
[30]	Qiu Min， Liu Da， Fu Qin. miR-129-5p shuttled by human synovial mesenchymal stem cell-derived exosomes relieves IL-1β induced osteoarthritis via targeting HMGB1［J］. Life Sci， 2021， 269： 118987. doi：10.1016/j.lfs.2020.118987 .
[31]	Klabukov I， Kisel A， Eygel D， et al. BMSC-derived exosomes attenuate rat osteoarthritis by regulating macrophage polarization through PINK1/parkin signaling pathway： Focus on immune responses in the perichondrium［J］. Cartilage， 2025： 19476035251348308. doi：10.1177/19476035251348308 .
[32]	Shen Xun， Qin Jian， Wei Zijian， et al. Bone marrow mesenchymal stem cell exosome-derived lncRNA TUC339 influences the progression of osteoarthritis by regulating synovial macrophage polarization and chondrocyte apoptosis［J］. Biomed Pharmacother， 2023， 167： 115488. doi：10.1016/j.biopha.2023.115488 .
[33]	Onorato F， Rucci M， Alessio-Mazzola M， et al. Autologous microfragmented adipose tissue treatment of knee osteoarthritis demonstrates effectiveness in 68% of patients at 4-year follow-up［J］. Arch Orthop Trauma Surg， 2024， 144（9）： 3925-3935. doi：10.1007/s00402-023-05143-y .
[34]	Bina V， Brancato A M， Caliogna L， et al. Mesenchymal stem cells and secretome as a new possible approach to treat cartilage damage： An in vitro study［J］. Biomolecules， 2024， 14（9）： 1068. doi：10.3390/biom14091068 .
[35]	Zhai Xiangyu， Zhang Hao， Xia Zhijia， et al. Oxytocin alleviates liver fibrosis via hepatic macrophages［J］. JHEP Rep， 2024， 6（6）： 101032. doi：10.1016/j.jhepr.2024.101032 .
[36]	Xie Hanghang， Xi Xiaowei， Lei Ting， et al. CD8⁺ T cell exhaustion in the tumor microenvironment of breast cancer［J］. Front Immunol， 2024， 15： 1507283. doi：10.3389/fimmu.2024.1507283 .
[37]	Li Yachen， Duan Junjun， Lin Weicheng， et al. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9［J］. Open Med （Wars）， 2023， 18（1）： 20230668. doi：10.1515/med-2023-0668 .
[38]	Wang Yiming， Fan Aoyuan， Lu Liangyu， et al. Exosome modification to better alleviates endoplasmic reticulum stress induced chondrocyte apoptosis and osteoarthritis［J］. Biochem Pharmacol， 2022， 206： 115343. doi：10.1016/j.bcp.2022.115343 .
[39]	Meng Chenyang， Na Yuyan， Han Changxu， et al. Exosomal miR-429 derived from adipose-derived stem cells ameliorated chondral injury in osteoarthritis via autophagy by targeting FEZ2［J］. Int Immunopharmacol， 2023， 120： 110315. doi：10.1016/j.intimp.2023.110315 .
[40]	Wang Jing， Li Jingzhi， He Xiuming， et al. Exosomal miRNA-25-3p from platelet-rich plasma alleviates chondrocyte pyroptosis and knee osteoarthritis by regulating MAP4K2/Hippo/TNFAIP3 pathway［J］. Funct Integr Genom， 2025， 25（1）： 268. doi：10.1007/s10142-025-01780-1 .
[41]	Dong Bingjiang， Liu Xinhui， Li Jiwei， 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. doi：10.1248/bpb.b22-00206 .
[42]	Song I， Glass N A， Sander E A， et al. The effect of exosome size in platelet-rich plasma on outcomes in patients treated for knee osteoarthritis［J］. Orthop J Sports Med， 2025， 13（9）： 23259671251360410. doi：10.1177/23259671251360410 .
[43]	Liu Zichang， Zhuang Yu， Fang Lianfei， et al. Breakthrough of extracellular vesicles in pathogenesis， diagnosis and treatment of osteoarthritis［J］. Bioact Mater， 2023， 22： 423-452. doi：10.1016/j.bioactmat.2022.10.012 .
[44]	Zhan Dong， Cross A， Wright H L， et al. Internalization of neutrophil-derived microvesicles modulates TNFα-stimulated proinflammatory cytokine production in human fibroblast-like synoviocytes［J］. Int J Mol Sci， 2021， 22（14）： 7409. doi：10.3390/ijms22147409 .
[45]	Ghosh P， Sasaki K， Pulido Ruiz I A， et al. Inflammatory macrophage to hepatocyte signals can be prevented by extracellular vesicle reprogramming［J］. J Cell Sci， 2023， 136（9）： jcs260691. doi：10.1242/jcs.260691 .
[46]	Kodidela S， Sinha N， Kumar A， et al. Extracellular vesicles released from macrophages modulates interleukin-1β in astrocytic and neuronal cells［J］. Sci Rep， 2023， 13（1）： 3005. doi：10.1038/s41598-023-29746-y .
[47]	Liu Bin， Xian Yansi， Chen Xiang， et al. Inflammatory fibroblast-like synoviocyte-derived exosomes aggravate osteoarthritis via enhancing macrophage glycolysis［J］. Adv Sci （Weinh）， 2024， 11（14）： e2307338. doi：10.1002/advs.202307338 .
[48]	Liu L， Fandiño J， Warren A J M， et al. Proinflammatory cytokine preconditioning enhances the therapeutic potency of different types of MSCs in inflammation［J］. Int J Mol Sci， 2026， 27（9）： 4090. doi：10.3390/ijms27094090 .
[49]	Nguyen T H， Dao H H， Duong C M， et al. Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes［J］. Front Immunol， 2022， 13： 1041592. doi：10.3389/fimmu.2022. 1041592 .
[50]	Jia Hao， Duan Lian， Yu Peng， et al. Digoxin ameliorates joint inflammatory microenvironment by downregulating synovial macrophage M1-like-polarization and its-derived exosomal miR-146b-5p/Usp3&Sox5 axis［J］. Int Immunopharmacol， 2022， 111： 109135. doi：10.1016/j.intimp.2022.109135 .
[51]	Xu Chen， Zhai Zanjing， Ying Hua， et al. Curcumin primed ADMSCs derived small extracellular vesicle exert enhanced protective effects on osteoarthritis by inhibiting oxidative stress and chondrocyte apoptosis［J］. J Nanobiotechnology， 2022， 20（1）： 123. doi：10.1186/s12951-022-01339-3 .
[52]	Shao Litao， Luo Liang， Qiu Jiehong， et al. PTH （1-34） enhances the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes by inhibiting proinflammatory cytokines expression on OA chondrocyte repair in vitro ［J］. Arthritis Res Ther， 2022， 24（1）： 96. doi：10.1186/s13075-022-02778-x .
[53]	Palamà M E F， Coco S， Shaw G M， et al. Xeno-free cultured mesenchymal stromal cells release extracellular vesicles with a “therapeutic” miRNA cargo ameliorating cartilage inflammation in vitro ［J］. Theranostics， 2023， 13（5）： 1470-1489. doi：10.7150/thno.77597 .
[54]	Chang Linghua， Wu Shucheng， Chen C H， et al. Exosomes derived from hypoxia-cultured human adipose stem cells alleviate articular chondrocyte inflammaging and post-traumatic osteoarthritis progression［J］. Int J Mol Sci， 2023， 24（17）： 13414. doi：10.3390/ijms241713414 .
[55]	Yang Yanmeng， Wu Yingnan， Yang Dahou， et al. Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles［J］. Bioact Mater， 2023， 27： 98-112. doi：10.1016/j.bioactmat.2023.03.017 .
[56]	陈少初，龚铭，张望，等. 缺氧下间充质干细胞分泌的外泌体对软骨细胞损伤的影响［J］. 实用医学杂志， 2025， 41（22）： 3529-3536. doi：10.3969/j.issn.1006-5725.2025.22.009 .
[57]	Xie Yong， Liu Quanbo， Tan Jinghua， et al. CAP-CD56⁺CD271⁺ BMSCs exos-loaded PVA/SA sustained-release hydrogel attenuates chondrocyte senescence and ameliorates lumbar facet joint osteoarthritis［J］. Bioact Mater， 2026， 57： 73-92. doi：10.1016/j.bioactmat.2025.10.027 .
[58]	Shang Kejia， Fu Chunxu， Li Ruxin， et al. Injectable hydrogel microspheres delivering cartilage-targeted LGR5-engineered exosomes for osteoarthritis therapy［J］. Mater Today Bio， 2026， 36： 102690. doi：10.1016/j.mtbio.2025.102690 .
[59]	Sakthi Mohan P， Abdul Majid N B， Susilo R J K， et al. Exosomal interventions in bone and osteochondral repair： Mechanisms and outcomes［J］. Int J Mol Sci， 2025， 26（22）： 11172. doi：10.3390/ijms262211172 .
[60]	Bolandnazar N S， Ahmad Raeissadat S， Haghighatkhah H， et al. Safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in knee osteoarthritis： A randomized， triple-blind， placebo-controlled clinical trial［J］. BMC Musculoskelet Disord， 2024， 25（1）： 856. doi：10.1186/s12891-024-07979-w .
[61]	Fu Pengjie， Luo Yan， Zheng Shengyuan， et al. The role of extracellular vesicles in musculoskeletal diseases［J］. J Extracell Vesicles， 2025， 14（11）： e70205. doi：10.1002/jev2.70205 .
[62]	González-Rodríguez A， De Toro F J， Jorge-Mora A， et al. Targeting osteoarthritis with small extracellular vesicle therapy： Potential and perspectives［J］. Front Bioeng Biotechnol， 2025， 13： 1570526. doi：10.3389/fbioe.2025.1570526 .
[63]	Clarke E J， Chabronova A， Peffers M J. Extracellular vesicles in cartilage homeostasis， osteoarthritis， and biomarker discovery［J］. Connect Tissue Res， 2025， 66（5）： 428-434. doi：10.1080/03008207.2025.2524064 .
[64]	Verma N， Arora S. Navigating the global regulatory landscape for exosome-based therapeutics： Challenges， strategies， and future directions［J］. Pharmaceutics， 2025， 17（8）： 990. doi：10.3390/pharmaceutics17080990 .
[65]	Wiest E F， Zubair A C. Generation of current good manufacturing practices-grade mesenchymal stromal cell-derived extracellular vesicles using automated bioreactors［J］. Biology， 2025， 14（3）： 313. doi：10.3390/biology14030313 .
[66]	Zhu K， Mao M， Li W， et al. A thermosensitive hydrogel delivery system incorporating wogonin-treated mesenchymal stromal cell （MSC）-derived exosomes alleviates osteoarthritis［J］. J Biol Eng， 2026. doi：10.1186/s13036-026-00709-x .
[67]	Deng Siyan， Chen Xi， Cao Hongfu， et al. Self-assembled bifunctional exosomes simplify chondrocyte-targeted sustained-release systems in decellularized cartilage microgels for synergistic osteoarthritis therapy［J］. Small， 2025， 21（38）： e03492. doi：10.1002/smll. 202503492 .
[68]	Sung S E， Seo M S， Park W T， et al. Extracellular vesicles： Their challenges and benefits as potential biomarkers for musculoskeletal disorders［J］. J Int Med Res， 2025， 53（2）： 3000605251317476. doi：10.1177/03000605251317476 .
[69]	Sun Chongxiao， Teng Fei， Xia Yayi. Extracellular vesicles in osteoarthritis： Mechanisms， therapeutic potential， and diagnostic applications［J］. Front Immunol， 2025， 16： 1595095. doi：10.3389/fimmu. 2025.1595095 .