Role of plant-derived exosome-like nanoparticle in osteoporosis and osteoarthritis_West China Medical Journal

Authors：

XIA Xianting ¹ , WANG Weiming ¹ , HUANG Haoqiang ² , PENG Zhijian ² , ZHANG Yili ³ ,  WANG Qing ²

1. Department of Orthopedics, Kunshan Sixth People’s Hospital, Kunshan, Jiangsu 215300, P. R. China;
2. Department of Orthopedics, Kunshan Hospital of Chinese Medicine, Kunshan, Jiangsu 215300, P. R. China;
3. College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P. R. China;

Corresponding author：

WANG Qing, Email: doctorwq1983@163.com

Keywords：

Plant-derived exosome-like nanoparticle; osteoporosis; osteoarthritis

DOI：

10.7507/1002-0179.202408079

Video：

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Abstract Full text Figures/Tables Video References Cited by

Plant-derived exosome-like nanoparticle (PELN) is a nanoscale vesicle secreted by plant cells, which has important biological functions. On the one hand, PELN can exert anti-osteoporosis (OP) effects by affecting the functions of osteoclasts, osteoblasts, and bone marrow mesenchymal stem cells. On the other hand, PELN can also inhibit inflammatory reactions, protect chondrocytes, and has potential value in treating osteoarthritis (OA). This article summarizes the basic concepts, formation and components, separation and characterization methods of PELN, and focuses on the intervention effect and molecular mechanism of PELN on OP and OA.

1.	Fan Y, Li Z, He Y. Exosomes in the pathogenesis, progression, and treatment of osteoarthritis. Bioengineering (Basel), 2022, 9(3): 99.
2.	Li QC, Li C, Zhang W, et al. Potential effects of exosomes and their microRNA carrier on osteoporosis. Curr Pharm Des, 2022, 28(11): 899-909.
3.	Mu N, Li J, Zeng L, et al. Plant-derived exosome-like nanovesicles: current progress and prospects. Int J Nanomedicine, 2023, 18: 4987-5009.
4.	Wang C, Xu M, Fan Q, et al. Therapeutic potential of exosome-based personalized delivery platform in chronic inflammatory diseases. Asian J Pharm Sci, 2023, 18(1): 100772.
5.	Liang B, Burley G, Lin S, et al. Osteoporosis pathogenesis and treatment: existing and emerging avenues. Cell Mol Biol Lett, 2022, 27(1): 72.
6.	张烽, 王斌, 曹蔼萱, 等. 原发性膝关节骨关节炎严重程度的危险因素分析. 中华创伤骨科杂志, 2024, 26(8): 698-704.
7.	Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis. Ann Phys Rehabil Med, 2016, 59(5/6): 333-339.
8.	《中国老年骨质疏松症诊疗指南 2023》工作组, 中国老年学和老年医学学会骨质疏松分会, 中国医疗保健国际交流促进会骨质疏松病学分会, 等. 中国老年骨质疏松症诊疗指南(2023). 中华骨与关节外科杂志, 2023, 16(10): 865-885.
9.	Zhang Y, Liu Y, Liu H, et al. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci, 2019, 9: 19.
10.	Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
11.	Cong M, Tan S, Li S, et al. Technology insight: plant-derived vesicles-how far from the clinical biotherapeutics and therapeutic drug carriers?. Adv Drug Deliv Rev, 2022, 182: 114108.
12.	Kim J, Li S, Zhang S, et al. Plant-derived exosome-like nanoparticles and their therapeutic activities. Asian J Pharm Sci, 2022, 17(1): 53-69.
13.	张雪萍, 鲁雨晴, 张月倩, 等. 植物细胞外囊泡及其分析技术的进展. 生物技术通报, 2023, 39(5): 32-43.
14.	Cui Y, Gao J, He Y, et al. Plant extracellular vesicles. Protoplasma, 2020, 257(1): 3-12.
15.	Subha D, Harshnii K, Madhikiruba KG, et al. Plant derived exosome-like nanovesicles: an updated overview. Plant Nano Biol, 2023, 3: 100022.
16.	Suharta S, Barlian A, Hidajah AC, et al. Plant-derived exosome-like nanoparticles: a concise review on its extraction methods, content, bioactivities, and potential as functional food ingredient. J Food Sci, 2021, 86(7): 2838-2850.
17.	Bai C, Liu J, Zhang X, et al. Research status and challenges of plant-derived exosome-like nanoparticles. Biomed Pharmacother, 2024, 174: 116543.
18.	Lian MQ, Chng WH, Liang J, et al. Plant-derived extracellular vesicles: recent advancements and current challenges on their use for biomedical applications. J Extracell Vesicles, 2022, 11(12): e12283.
19.	He B, Cai Q, Qiao L, et al. RNA-binding proteins contribute to small RNA loading in plant extracellular vesicles. Nat Plants, 2021, 7(3): 342-352.
20.	潘林思, 王文彩, 姚孟宇, 等. 植物源外泌体样纳米颗粒及其应用研究进展. 中国中药杂志, 2023, 48(22): 5977-5984.
21.	Lu X, Han Q, Chen J, et al. Celery (Apium graveolens L. ) exosome-like nanovesicles as a new-generation chemotherapy drug delivery platform against tumor proliferation. J Agric Food Chem, 2023, 71(22): 8413-8424.
22.	赵梦, 李思敏, 张蕾, 等. 植物来源囊泡及其生物医学应用研究进展. 药学学报, 2021, 56(8): 2039-2047.
23.	张馨月, 胡克. 植物外泌体的抗炎抗癌机制研究进展. 武汉大学学报(医学版), 2023, 44(11): 1410-1414.
24.	Wang H, Luo Y, Wang H, et al. Mechanistic advances in osteoporosis and anti-osteoporosis therapies. MedComm (2020), 2023, 4(3): e244.
25.	Oryan A, Sahvieh S. Effects of bisphosphonates on osteoporosis: focus on zoledronate. Life Sci, 2021, 264: 118681.
26.	Pu H, Wen X, Luo D, et al. Regulation of progesterone receptor expression in endometriosis, endometrial cancer, and breast cancer by estrogen, polymorphisms, transcription factors, epigenetic alterations, and ubiquitin-proteasome system. J Steroid Biochem Mol Biol, 2023, 227: 106199.
27.	Yang LY, Li CQ, Zhang YL, et al. Emerging drug delivery vectors: engineering of plant-derived nanovesicles and their applications in biomedicine. Int J Nanomedicine, 2024, 19: 2591-2610.
28.	Takayanagi H. RANKL as the master regulator of osteoclast differentiation. J Bone Miner Metab, 2021, 39(1): 13-18.
29.	Seo K, Yoo JH, Kim J, et al. Ginseng-derived exosome-like nanovesicles extracted by sucrose gradient ultracentrifugation to inhibit osteoclast differentiation. Nanoscale, 2023, 15(12): 5798-5808.
30.	Ingwersen LC, Frank M, Naujokat H, et al. BMP-2 long-term stimulation of human pre-osteoblasts induces osteogenic differentiation and promotes transdifferentiation and bone remodeling processes. Int J Mol Sci, 2022, 23(6): 3077.
31.	Hwang JH, Park YS, Kim HS, et al. Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice. J Control Release, 2023, 355: 184-198.
32.	Sim Y, Seo HJ, Kim DH, et al. The effect of apple-derived nanovesicles on the osteoblastogenesis of osteoblastic MC3T3-E1 cells. J Med Food, 2023, 26(1): 49-58.
33.	Park YS, Kim HW, Hwang JH, et al. Plum-derived exosome-like nanovesicles induce differentiation of osteoblasts and reduction of osteoclast activation. Nutrients, 2023, 15(9): 2107.
34.	Qadir A, Liang S, Wu Z, et al. Senile osteoporosis: the involvement of differentiation and senescence of bone marrow stromal cells. Int J Mol Sci, 2020, 21(1): 349.
35.	Zhao Q, Feng J, Liu F, et al. Rhizoma drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling. Acta Pharm Sin B, 2024, 14(5): 2210-2227.
36.	Zhan W, Deng M, Huang X, et al. Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhacning autophagy. J Control Release, 2023, 364: 644-653.
37.	Perut F, Roncuzzi L, Avnet S, et al. Strawberry-derived exosome-like nanoparticles prevent oxidative stress in human mesenchymal stromal cells. Biomolecules, 2021, 11(1): 87.
38.	Gupta R, Gupta S, Gupta P, et al. Establishing the callus-based isolation of extracellular vesicles from cissus quadrangularis and elucidating their role in osteogenic differentiation. J Funct Biomater, 2023, 14(11): 540.
39.	Cucchiarini M, de Girolamo L, Filardo G, et al. Basic science of osteoarthritis. J Exp Orthop, 2016, 3(1): 22.
40.	Mao X, Li T, Qi W, et al. Advances in the study of plant-derived extracellular vesicles in the skeletal muscle system. Pharmacol Res, 2024, 204: 107202.
41.	Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage, 2013, 21(1): 16-21.
42.	Chow YY, Chin KY. The role of inflammation in the pathogenesis of osteoarthritis. Mediators Inflamm, 2020, 2020: 8293921.
43.	Yi Q, Xu Z, Thakur A, et al. Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment. Pharmacol Res, 2023, 190: 106733.
44.	Kim J, Zhang S, Zhu Y, et al. Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of inflammatory cytokines. J Ginseng Res, 2023, 47(5): 627-637.
45.	Vanessa V, Rachmawati H, Barlian A. Anti-inflammatory potential of goldenberry-derived exosome-like nanoparticles in macrophage polarization. Future Sci OA, 2024, 10(1): FSO943.
46.	Emmanuela N, Muhammad DR, Iriawati, et al. Isolation of plant-derived exosome-like nanoparticles (PDENs) from Solanum nigrum L. berries and their effect on interleukin-6 expression as a potential anti-inflammatory agent. PLoS One, 2024, 19(1): e0296259.
47.	Iriawati I, Vitasasti S, Rahmadian FNA, et al. Isolation and characterization of plant-derived exosome-like nanoparticles from Carica papaya L. fruit and their potential as anti-inflammatory agent. PLoS One, 2024, 19(7): e0304335.
48.	Wei Y, Cai X, Wu Q, et al. Extraction, isolation, and component analysis of turmeric-derived exosome-like nanoparticles. Bioengineering (Basel), 2023, 10(10): 1199.
49.	Qiu B, Xu X, Yi P, et al. Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124/NF-κB and miR-143/ROCK1/TLR9 signalling pathways. J Cell Mol Med, 2020, 24(18): 10855-10865.
50.	Sen CK, Ghatak S. miRNA control of tissue repair and regeneration. Am J Pathol, 2015, 185(10): 2629-2640.
51.	Sarasati A, Syahruddin MH, Nuryanti A, et al. Plant-derived exosome-like nanoparticles for biomedical applications and regenerative therapy. Biomedicines, 2023, 11(4): 1053.
52.	Yıldırım M, Ünsal N, Kabataş B, et al. Effect of solanum lycopersicum and citrus limon-derived exosome-like vesicles on chondrogenic differentiation of adipose-derived stem cells. Appl Biochem Biotechnol, 2024, 196(1): 203-219.
53.	Chen P, Liu X, Gu C, et al. A plant-derived natural photosynthetic system for improving cell anabolism. Nature, 2022, 612(7940): 546-554.
54.	Ni Z, Zhou S, Li S, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res, 2020, 8: 25.
55.	Rudiansyah M, El-Sehrawy AA, Ahmad I, et al. Osteoporosis treatment by mesenchymal stromal/stem cells and their exosomes: emphasis on signaling pathways and mechanisms. Life Sci, 2022, 306: 120717.
56.	Zhang L, Wang Q, Su H, et al. Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts. J Biosci Bioeng, 2021, 131(6): 671-678.
57.	Cui Y, Guo Y, Kong L, et al. A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis. Bioact Mater, 2021, 10: 207-221.
58.	Liang Y, Xu X, Li X, et al. Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy. ACS Appl Mater Interfaces, 2020, 12(33): 36938-36947.
59.	Logozzi M, Di Raimo R, Mizzoni D, et al. The potentiality of plant-derived nanovesicles in human health-a comparison with human exosomes and artificial nanoparticles. Int J Mol Sci, 2022, 23(9): 4919.
60.	Liu Y, Ren C, Zhan R, et al. Exploring the potential of plant-derived exosome-like nanovesicle as functional food components for human health: a review. Foods, 2024, 13(5): 712.
61.	汪青, 黄昊强, 陈勇, 等. 二仙汤在绝经后骨质疏松症肾阳虚证治疗中的应用价值及作用机制研究. 中医正骨, 2022, 34(3): 8-14.
62.	Huang H, Feng X, Feng Y, et al. Bone-targeting HUVEC-derived exosomes containing miR-503-5p for osteoporosis therapy. ACS Appl Nano Mater, 2023, 7(1): 1156-1169.
63.	Song H, Li X, Zhao Z, et al. Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes. Nano Lett, 2019, 19(5): 3040-3048.

1. Fan Y, Li Z, He Y. Exosomes in the pathogenesis, progression, and treatment of osteoarthritis. Bioengineering (Basel), 2022, 9(3): 99.
2. Li QC, Li C, Zhang W, et al. Potential effects of exosomes and their microRNA carrier on osteoporosis. Curr Pharm Des, 2022, 28(11): 899-909.
3. Mu N, Li J, Zeng L, et al. Plant-derived exosome-like nanovesicles: current progress and prospects. Int J Nanomedicine, 2023, 18: 4987-5009.
4. Wang C, Xu M, Fan Q, et al. Therapeutic potential of exosome-based personalized delivery platform in chronic inflammatory diseases. Asian J Pharm Sci, 2023, 18(1): 100772.
5. Liang B, Burley G, Lin S, et al. Osteoporosis pathogenesis and treatment: existing and emerging avenues. Cell Mol Biol Lett, 2022, 27(1): 72.
6. 张烽, 王斌, 曹蔼萱, 等. 原发性膝关节骨关节炎严重程度的危险因素分析. 中华创伤骨科杂志, 2024, 26(8): 698-704.
7. Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis. Ann Phys Rehabil Med, 2016, 59(5/6): 333-339.
8. 《中国老年骨质疏松症诊疗指南 2023》工作组, 中国老年学和老年医学学会骨质疏松分会, 中国医疗保健国际交流促进会骨质疏松病学分会, 等. 中国老年骨质疏松症诊疗指南(2023). 中华骨与关节外科杂志, 2023, 16(10): 865-885.
9. Zhang Y, Liu Y, Liu H, et al. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci, 2019, 9: 19.
10. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
11. Cong M, Tan S, Li S, et al. Technology insight: plant-derived vesicles-how far from the clinical biotherapeutics and therapeutic drug carriers?. Adv Drug Deliv Rev, 2022, 182: 114108.
12. Kim J, Li S, Zhang S, et al. Plant-derived exosome-like nanoparticles and their therapeutic activities. Asian J Pharm Sci, 2022, 17(1): 53-69.
13. 张雪萍, 鲁雨晴, 张月倩, 等. 植物细胞外囊泡及其分析技术的进展. 生物技术通报, 2023, 39(5): 32-43.
14. Cui Y, Gao J, He Y, et al. Plant extracellular vesicles. Protoplasma, 2020, 257(1): 3-12.
15. Subha D, Harshnii K, Madhikiruba KG, et al. Plant derived exosome-like nanovesicles: an updated overview. Plant Nano Biol, 2023, 3: 100022.
16. Suharta S, Barlian A, Hidajah AC, et al. Plant-derived exosome-like nanoparticles: a concise review on its extraction methods, content, bioactivities, and potential as functional food ingredient. J Food Sci, 2021, 86(7): 2838-2850.
17. Bai C, Liu J, Zhang X, et al. Research status and challenges of plant-derived exosome-like nanoparticles. Biomed Pharmacother, 2024, 174: 116543.
18. Lian MQ, Chng WH, Liang J, et al. Plant-derived extracellular vesicles: recent advancements and current challenges on their use for biomedical applications. J Extracell Vesicles, 2022, 11(12): e12283.
19. He B, Cai Q, Qiao L, et al. RNA-binding proteins contribute to small RNA loading in plant extracellular vesicles. Nat Plants, 2021, 7(3): 342-352.
20. 潘林思, 王文彩, 姚孟宇, 等. 植物源外泌体样纳米颗粒及其应用研究进展. 中国中药杂志, 2023, 48(22): 5977-5984.
21. Lu X, Han Q, Chen J, et al. Celery (Apium graveolens L. ) exosome-like nanovesicles as a new-generation chemotherapy drug delivery platform against tumor proliferation. J Agric Food Chem, 2023, 71(22): 8413-8424.
22. 赵梦, 李思敏, 张蕾, 等. 植物来源囊泡及其生物医学应用研究进展. 药学学报, 2021, 56(8): 2039-2047.
23. 张馨月, 胡克. 植物外泌体的抗炎抗癌机制研究进展. 武汉大学学报(医学版), 2023, 44(11): 1410-1414.
24. Wang H, Luo Y, Wang H, et al. Mechanistic advances in osteoporosis and anti-osteoporosis therapies. MedComm (2020), 2023, 4(3): e244.
25. Oryan A, Sahvieh S. Effects of bisphosphonates on osteoporosis: focus on zoledronate. Life Sci, 2021, 264: 118681.
26. Pu H, Wen X, Luo D, et al. Regulation of progesterone receptor expression in endometriosis, endometrial cancer, and breast cancer by estrogen, polymorphisms, transcription factors, epigenetic alterations, and ubiquitin-proteasome system. J Steroid Biochem Mol Biol, 2023, 227: 106199.
27. Yang LY, Li CQ, Zhang YL, et al. Emerging drug delivery vectors: engineering of plant-derived nanovesicles and their applications in biomedicine. Int J Nanomedicine, 2024, 19: 2591-2610.
28. Takayanagi H. RANKL as the master regulator of osteoclast differentiation. J Bone Miner Metab, 2021, 39(1): 13-18.
29. Seo K, Yoo JH, Kim J, et al. Ginseng-derived exosome-like nanovesicles extracted by sucrose gradient ultracentrifugation to inhibit osteoclast differentiation. Nanoscale, 2023, 15(12): 5798-5808.
30. Ingwersen LC, Frank M, Naujokat H, et al. BMP-2 long-term stimulation of human pre-osteoblasts induces osteogenic differentiation and promotes transdifferentiation and bone remodeling processes. Int J Mol Sci, 2022, 23(6): 3077.
31. Hwang JH, Park YS, Kim HS, et al. Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice. J Control Release, 2023, 355: 184-198.
32. Sim Y, Seo HJ, Kim DH, et al. The effect of apple-derived nanovesicles on the osteoblastogenesis of osteoblastic MC3T3-E1 cells. J Med Food, 2023, 26(1): 49-58.
33. Park YS, Kim HW, Hwang JH, et al. Plum-derived exosome-like nanovesicles induce differentiation of osteoblasts and reduction of osteoclast activation. Nutrients, 2023, 15(9): 2107.
34. Qadir A, Liang S, Wu Z, et al. Senile osteoporosis: the involvement of differentiation and senescence of bone marrow stromal cells. Int J Mol Sci, 2020, 21(1): 349.
35. Zhao Q, Feng J, Liu F, et al. Rhizoma drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling. Acta Pharm Sin B, 2024, 14(5): 2210-2227.
36. Zhan W, Deng M, Huang X, et al. Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhacning autophagy. J Control Release, 2023, 364: 644-653.
37. Perut F, Roncuzzi L, Avnet S, et al. Strawberry-derived exosome-like nanoparticles prevent oxidative stress in human mesenchymal stromal cells. Biomolecules, 2021, 11(1): 87.
38. Gupta R, Gupta S, Gupta P, et al. Establishing the callus-based isolation of extracellular vesicles from cissus quadrangularis and elucidating their role in osteogenic differentiation. J Funct Biomater, 2023, 14(11): 540.
39. Cucchiarini M, de Girolamo L, Filardo G, et al. Basic science of osteoarthritis. J Exp Orthop, 2016, 3(1): 22.
40. Mao X, Li T, Qi W, et al. Advances in the study of plant-derived extracellular vesicles in the skeletal muscle system. Pharmacol Res, 2024, 204: 107202.
41. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage, 2013, 21(1): 16-21.
42. Chow YY, Chin KY. The role of inflammation in the pathogenesis of osteoarthritis. Mediators Inflamm, 2020, 2020: 8293921.
43. Yi Q, Xu Z, Thakur A, et al. Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment. Pharmacol Res, 2023, 190: 106733.
44. Kim J, Zhang S, Zhu Y, et al. Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of inflammatory cytokines. J Ginseng Res, 2023, 47(5): 627-637.
45. Vanessa V, Rachmawati H, Barlian A. Anti-inflammatory potential of goldenberry-derived exosome-like nanoparticles in macrophage polarization. Future Sci OA, 2024, 10(1): FSO943.
46. Emmanuela N, Muhammad DR, Iriawati, et al. Isolation of plant-derived exosome-like nanoparticles (PDENs) from Solanum nigrum L. berries and their effect on interleukin-6 expression as a potential anti-inflammatory agent. PLoS One, 2024, 19(1): e0296259.
47. Iriawati I, Vitasasti S, Rahmadian FNA, et al. Isolation and characterization of plant-derived exosome-like nanoparticles from Carica papaya L. fruit and their potential as anti-inflammatory agent. PLoS One, 2024, 19(7): e0304335.
48. Wei Y, Cai X, Wu Q, et al. Extraction, isolation, and component analysis of turmeric-derived exosome-like nanoparticles. Bioengineering (Basel), 2023, 10(10): 1199.
49. Qiu B, Xu X, Yi P, et al. Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124/NF-κB and miR-143/ROCK1/TLR9 signalling pathways. J Cell Mol Med, 2020, 24(18): 10855-10865.
50. Sen CK, Ghatak S. miRNA control of tissue repair and regeneration. Am J Pathol, 2015, 185(10): 2629-2640.
51. Sarasati A, Syahruddin MH, Nuryanti A, et al. Plant-derived exosome-like nanoparticles for biomedical applications and regenerative therapy. Biomedicines, 2023, 11(4): 1053.
52. Yıldırım M, Ünsal N, Kabataş B, et al. Effect of solanum lycopersicum and citrus limon-derived exosome-like vesicles on chondrogenic differentiation of adipose-derived stem cells. Appl Biochem Biotechnol, 2024, 196(1): 203-219.
53. Chen P, Liu X, Gu C, et al. A plant-derived natural photosynthetic system for improving cell anabolism. Nature, 2022, 612(7940): 546-554.
54. Ni Z, Zhou S, Li S, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res, 2020, 8: 25.
55. Rudiansyah M, El-Sehrawy AA, Ahmad I, et al. Osteoporosis treatment by mesenchymal stromal/stem cells and their exosomes: emphasis on signaling pathways and mechanisms. Life Sci, 2022, 306: 120717.
56. Zhang L, Wang Q, Su H, et al. Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts. J Biosci Bioeng, 2021, 131(6): 671-678.
57. Cui Y, Guo Y, Kong L, et al. A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis. Bioact Mater, 2021, 10: 207-221.
58. Liang Y, Xu X, Li X, et al. Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy. ACS Appl Mater Interfaces, 2020, 12(33): 36938-36947.
59. Logozzi M, Di Raimo R, Mizzoni D, et al. The potentiality of plant-derived nanovesicles in human health-a comparison with human exosomes and artificial nanoparticles. Int J Mol Sci, 2022, 23(9): 4919.
60. Liu Y, Ren C, Zhan R, et al. Exploring the potential of plant-derived exosome-like nanovesicle as functional food components for human health: a review. Foods, 2024, 13(5): 712.
61. 汪青, 黄昊强, 陈勇, 等. 二仙汤在绝经后骨质疏松症肾阳虚证治疗中的应用价值及作用机制研究. 中医正骨, 2022, 34(3): 8-14.
62. Huang H, Feng X, Feng Y, et al. Bone-targeting HUVEC-derived exosomes containing miR-503-5p for osteoporosis therapy. ACS Appl Nano Mater, 2023, 7(1): 1156-1169.
63. Song H, Li X, Zhao Z, et al. Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes. Nano Lett, 2019, 19(5): 3040-3048.

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