<scp>ATF4</scp>‐modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy

Wang, Yan; He, Shi-Hao; Liang, Xu; Zhang, Xinxin; Li, Shanshan; Li, Tian-Fang

doi:10.1002/iub.2414

Cited by 26 publications

(25 citation statements)

References 24 publications

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“…Activated transcription factor 4 (ATF4) is essential for chondrocyte proliferation and bone formation. Wang et al introduced ATF4 mRNA into serum-derived EVs from OA mice (OA-EVs) by electroporation, and found ATF4-modified OA-EVs can protect cartilage and alleviate OA progression by inducing autophagy [ 60 ].…”

Section: Cell Pretreatment Strategymentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

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Section: Cell Pretreatment Strategymentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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“… 101 Valadi et al 102 were the first to discover the presence of mRNAs and miRNAs in exosomes, and indicated that exosomes could modify the protein production and gene expression of target cells by transferring exosomal mRNAs or miRNAs. Wang et al 80 investigated the therapeutic effect of the activating transcription factor 4 ( ATF4 ) gene in cartilage regeneration by introducing ATF4 mRNA into exosomes via electroporation. The effects of exosomes derived from OA serum (OA-Exos) and ATF4 mRNA-overexpressing exosomes (ATF4-OA-Exos) were compared, and showed that the ATF4-OA-Exos were more potent compared to the OA-Exos in preventing and alleviating cartilage degeneration via the stimulation of autophagy.…”

Section: Resultsmentioning

confidence: 99%

“…Currently, it remains unclear if multiple injections are more effective compared to single injection for promoting cartilage regeneration, as none of the studies compared the therapeutic effect of single and multiple injections. Cosenza et al 74 and Wang et al 80 showed that the effect of exosomes from a single intra-articular injection may be month-long. This is most probably due to the direct exosome administration to the target site (cartilage is avascular and alymphatic; thus, the clearance of the injected exosomes is slower) and the exosomes might induce cellular reprogramming and remodel resident or injured cells by activating regenerative mechanisms by transferring bioactive molecules.…”

Section: Resultsmentioning

confidence: 99%

“…Exo group: BM-MSC-Exos 2. pExo group: polydactyly BM-MSC-Exos 3. OA group: Saline 4.Normal control Day 28 post-collagenase VII injection Not reported Not reported ● pExo group alleviated cartilage damage evidenced by the significant lower OARSI scores than the OA and Exo groups Not reported Wang et al 80 C57BL/6J mice Surgically induced OA Single intra-articular injection at week 4 post-operation 1. Sham-Exo group: 200 µg sham-Exos 2.…”

Section: Resultsmentioning

confidence: 99%

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Potential of Exosomes as Cell-Free Therapy in Articular Cartilage Regeneration: A Review

Ng¹,

Chai²,

Foo³

et al. 2021

IJN

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Treatment of cartilage defects such as osteoarthritis (OA) and osteochondral defect (OCD) remains a huge clinical challenge in orthopedics. OA is one of the most common chronic health conditions and is mainly characterized by the degeneration of articular cartilage, shown in the limited capacity for intrinsic repair. OCD refers to the focal defects affecting cartilage and the underlying bone. The current OA and OCD management modalities focus on symptom control and on improving joint functionality and the patient’s quality of life. Cell-based therapy has been evaluated for managing OA and OCD, and its chondroprotective efficacy is recognized mainly through paracrine action. Hence, there is growing interest in exploiting extracellular vesicles to induce cartilage regeneration. In this review, we explore the in vivo evidence of exosomes on cartilage regeneration. A total of 29 in vivo studies from the PubMed and Scopus databases were identified and analyzed. The studies reported promising results in terms of in vivo exosome delivery and uptake; improved cartilage morphological, histological, and biochemical outcomes; enhanced subchondral bone regeneration; and improved pain behavior following exosome treatment. In addition, exosome therapy is safe, as the included studies documented no significant complications. Modifying exosomal cargos further increased the cartilage and subchondral bone regeneration capacity of exosomes. We conclude that exosome administration is a potent cell-free therapy for alleviating OA and OCD. However, additional studies are needed to confirm the therapeutic potential of exosomes and to identify the standard protocol for exosome-based therapy in OA and OCD management.

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“…Furthermore, ATF4-OA-Exosomes promote the autophagy and inhibit the apoptosis in TNF-α or tunicamycin treated chondrocytes (Wang Y. et al, 2021).…”

Section: Exosomes Derived From Primary Chondrocytesmentioning

confidence: 94%

The Research Progress of Exosomes in Osteoarthritis, With Particular Emphasis on the Mediating Roles of miRNAs and lncRNAs

et al. 2021

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Osteoarthritis (OA) is a kind of degenerative disease, which is caused by many factors such as aging, obesity, strain, trauma, congenital joint abnormalities, joint deformities. Exosomes are mainly derived from the invagination of intracellular lysosomes, which are released into the extracellular matrix after fusion of the outer membrane of multi vesicles with the cell membrane. Exosomes mediate intercellular communication and regulate the biological activity of receptor cells by carrying non-coding RNA, long noncoding RNAs (lncRNAs), microRNAs (miRNAs), proteins and lipids. Evidences show that exosomes are involved in the pathogenesis of OA. In view of the important roles of exosomes in OA, this paper systematically reviewed the roles of exosomes in the pathogenesis of OA, including the roles of exosomes in OA diagnosis, the regulatory mechanisms of exosomes in the pathogenesis, and the intervention roles of exosomes in the treatment of OA. Reviewing the roles of exosomes in OA will help to clarify the pathogenesis of OA and explore new diagnostic biomarkers and therapeutic targets.

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ATF4‐modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy

Cited by 26 publications

References 24 publications

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

Potential of Exosomes as Cell-Free Therapy in Articular Cartilage Regeneration: A Review

The Research Progress of Exosomes in Osteoarthritis, With Particular Emphasis on the Mediating Roles of miRNAs and lncRNAs

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