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Exosomes are small nano-sized extracellular vesicles secreted by cells that play a role in physiological and pathological processes in the human body by carrying other bioactive substances such as nucleic acids and proteins. They can transfer biochemical molecules into target cells and mediate biological processes by regulating target genes and proteins. Exosomes are involved in inflammation, immune regulation, neovascularization and cartilage repair in osteoarthritis, therefore, the application of exosomes to osteoarthritis may open up new horizons for the diagnosis and treatment of osteoarthritis[1].

Micro-RNAs are single-stranded non-coding RNAs of 19 to 25 nucleotides in length, which can affect various cellular processes and play important roles in various diseases [2]. MiRNAs have been shown to regulate different cellular processes in different diseases, such as mediating the Wnt/β-catenin pathway to regulate the metabolic activity of chondrocytes and osteoblasts, which provides a new theoretical basis for the use of miRNAs as therapeutic drugs for osteoarthritis [3]. Exosomes play a role in cartilage regeneration by carrying miRNAs that promote chondrocyte proliferation and matrix secretion, reducing scar tissue formation and inflammation. Therefore, in-depth exploration and elaboration of the mechanisms of exosomes and miRNAs in the diagnosis and treatment of osteoarthritis provide new research targets for osteoarthritis.

Bone marrow mesenchymal stem cells have the potential for multidirectional differentiation and self-renewal, and can differentiate into osteoblasts, chondrocytes, and adipocytes. They can also perform functions such as tissue repair through paracrine mechanisms [4]. Bone marrow mesenchymal stem cell-derived exosomes can play a therapeutic role by carrying miRNAs, thus solving important problems in clinical disease treatment and tissue engineering research. Tao Yunxia et al [5] found that bone marrow mesenchymal stem cell-derived exosomes can down-regulate DDX20 and inactivate the nuclear transcription factor NF-κB signaling pathway by carrying miRNA-361-5p, and ultimately alleviate the symptoms of osteoarthritis. Bone marrow mesenchymal stem cell-derived exosome-derived miR-206 can promote the proliferation and differentiation of osteoblasts in osteoarthritis by reducing the E74-like ETS transcription factor 3 (Elf3), providing a new target for osteoarthritis treatment. Bone marrow mesenchymal stem cell-derived exosomes overexpressing miR-26a-5p can act as an inhibitor of synovial fibroblast damage by prostaglandin-endoperoxidesynthase 2 (PTGS2) in osteoarthritis [6]. Upregulation of syndecan-1 (SDC-1), a target gene of miR-9-5p, leads to increased inflammation and osteoarthritis-like injury, and the bone marrow mesenchymal stem cell-derived exosome miR-9-5p protects cartilage by inhibiting SDC1 [7].

The infrapatellar fat pad is simple and easy to obtain in clinical knee surgery. Mesenchymal stem cell-derived exosomes of the infrapatellar fat pad carry large amounts ofmiRNA-100-5p, which can activate the mTOR autophagy signaling pathway, inhibit apoptosis, enhance matrix synthesis, reduce the expression of catabolic factors in vitro, thereby protecting articular cartilage and improving the symptoms of gait abnormalities [8]

Urinary stem cells have also received attention from researchers because of their wide source and their ability to modulate the course of osteoarthritis. Liu Yuan et al [9] found that by injecting human urothelial stem cell-derived exosomes into the joints of an IL-1β-treated osteoarthritis rat model, chondrocyte proliferation and migration were enhanced, apoptosis was inhibited, and extracellular matrix secretion was reduced. When human urothelial stem cells were transfected with lentiviral particles carrying miR-140-5p and exosomes secreted from these cells were collected and injected into the same rat model of osteoarthritis, it was found that exosomes carrying miR-140-5p not only enhanced cartilage regeneration and subchondral bone remodeling, but also increased extracellular matrix secretion by targeting the vascular endothelial growth factor VEGFA.

Reference:

  1. Cao H, Li W, Zhang H, Hong L, Feng X, Gao X, Li H, Lv N, Liu M. Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment. J Nanobiotechnology. 2024 May 20;22(1):271.

  2. Gao Y, Patil S, Qian A. The Role of MicroRNAs in Bone Metabolism and Disease. Int J Mol Sci. 2020 Aug 24;21(17):6081.

  3. Shang X, Böker KO, Taheri S, Hawellek T, Lehmann W, Schilling AF. The Interaction between microRNAs and the Wnt/β-Catenin Signaling Pathway in Osteoarthritis. Int J Mol Sci. 2021 Sep 13;22(18):9887.

  4. Wang Z, Wu Y, Zhao Z, Liu C, Zhang L. Study on Transorgan Regulation of Intervertebral Disc and Extra-Skeletal Organs Through Exosomes Derived From Bone Marrow Mesenchymal Stem Cells. Front Cell Dev Biol. 2021 Sep 23;9:741183.

  5. Tao Y, Zhou J, Wang Z, Tao H, Bai J, Ge G, Li W, Zhang W, Hao Y, Yang X, Geng D. Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-κB signaling pathway. Bioorg Chem. 2021 Aug;113:104978.

  6. Huang Y, Zhang X, Zhan J, Yan Z, Chen D, Xue X, Pan X. Bone marrow mesenchymal stem cell-derived exosomal miR-206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3. J Cell Mol Med. 2021 Aug;25(16):7734-7745.

  7. Jin Z, Ren J, Qi S. Exosomal miR-9-5p secreted by bone marrow-derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1. Cell Tissue Res. 2020 Jul;381(1):99-114.

  8. Wu J, Kuang L, Chen C, Yang J, Zeng WN, Li T, Chen H, Huang S, Fu Z, Li J, Liu R, Ni Z, Chen L, Yang L. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials. 2019 Jun;206:87-100.

  9. Liu Y, Zeng Y, Si HB, Tang L, Xie HQ, Shen B. Exosomes Derived From Human Urine-Derived Stem Cells Overexpressing miR-140-5p Alleviate Knee Osteoarthritis Through Downregulation of VEGFA in a Rat Model. Am J Sports Med. 2022 Mar;50(4):1088-1105.