Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

Zhou, Quan-fa; Cai, Youzhi; Jiang, Yangzi; Lin, Xiaoyan

doi:10.7150/ijbs.41637

Cited by 52 publications

(21 citation statements)

References 72 publications

(95 reference statements)

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“…Synovial fluid can be monitored to assess pathophysiological alterations in the knee joint space, as it is closely associated with the articular cartilage and the synovial membrane in this tissue site 32 , 33 . Cell-derived exosomes represent particularly promising tools for diagnostic biomarker identification when evaluating disease progression, as they can both reflect and influence pathophysiological conditions within a given microenvironmental setting 34 , 35 . Herein, we, therefore, conducted an analysis of miRNAs within exosomes derived from the synovial fluid of OA and control patients.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

Zhou

Jiang

et al. 2021

Cell Death Discov.

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MicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

Zhou

Jiang

et al. 2021

Cell Death Discov.

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“…A few studies have confirmed that EVs from patients with an osteoarthritic joint were significantly different from normal patients (Barile and Vassalli, 2017 ; Zhang et al, 2017 ; Zhou Q. et al, 2020 ) ( Figure 3 ). For instance, significantly elevated concentrations of LncRNA PCGEM1 were detected in synovial fluid from patients with OA (Zhao and Xu, 2018 ).…”

Section: Changes In Evs To Reflect the Joint Diseasementioning

confidence: 82%

Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases

Qiao

Chen

Cao

et al. 2021

Front. Bioeng. Biotechnol.

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Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.

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“…In this aspect, MSC-derived exosomes have proven to be valuable as they can exert an anti-inflammatory response. For example, adipose MSC-derived exosomes could decrease levels of pro-inflammatory mediators, reducing stimulation of NF-κB and activator protein 1 while increasing expression of anti-inflammatory cytokines and the expression of miR-100-5p, which binds to 3 UTR of mTOR to augment autophagy activity [8,111]. With similar mechanisms, exosomes isolated from bone marrow-derived MSCs [112] and umbilical-cord-derived MSCs [113] were able to relieve the pathological Pharmaceuticals 2021, 14, 1093 9 of 25 characteristics in diseased joints through decreasing the infiltration of inflammatory cells as well as repressing levels of inflammatory factors [114].…”

Section: Promoting Cartilage Repair Using Exosomesmentioning

confidence: 99%

“…In particular, exosomes, a type of small extracellular vesicle (EV) secreted by cells for intercellular communication, have become the focus of recent studies. Exosomes are rich in proteins, lipids, and nucleic acids and have been documented to promote cartilage regeneration [7,8]. Previously, a battery of miRNAs was found to be involved in cartilage regeneration [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes and MicroRNAs in Cartilage Regeneration: Biogenesis, Efficacy, miRNA Enrichment and Delivery

et al. 2021

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Exosomes are the small extracellular vesicles secreted by cells for intercellular communication. Exosomes are rich in therapeutic cargos such as microRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids. Recently, many studies have focused on miRNAs as a promising therapeutic factor to support cartilage regeneration. Exosomes are known to contain a substantial amount of a variety of miRNAs. miRNAs regulate the post-transcriptional gene expression by base-pairing with the target messenger RNA (mRNA), leading to gene silencing. Several exosomal miRNAs have been found to play a role in cartilage regeneration by promoting chondrocyte proliferation and matrix secretion, reducing scar tissue formation, and subsiding inflammation. The exosomal miRNA cargo can be modulated using techniques such as cell transfection and priming as well as post-secretion modifications to upregulate specific miRNAs to enhance the therapeutic effect. Exosomes are delivered to the joints through direct injection or via encapsulation within a scaffold for sustained release. To date, exosome therapy for cartilage injuries has yet to be optimized as the ideal cell source for exosomes, and the dose and method of delivery have yet to be identified. More importantly, a deeper understanding of the role of exosomal miRNAs in cartilage repair is paramount for the development of more effective exosome therapy.

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Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

Cited by 52 publications

References 72 publications

Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases

Mesenchymal Stem Cell-Derived Exosomes and MicroRNAs in Cartilage Regeneration: Biogenesis, Efficacy, miRNA Enrichment and Delivery

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