Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis

Tao, Shi‐Cong; Huang, Ji-Yan; Gao, Yuan; Li, Zixiang; Wei, Zhanying; Dawes, Helen; Guo, Sheng

doi:10.1016/j.bioactmat.2021.04.031

Cited by 92 publications

(66 citation statements)

References 80 publications

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“…After articular cartilage injury, the force absorption effect decreases, resulting in the progressive deterioration of joint performance ( Elder and Athanasiou, 2009 ). An imbalance in the anabolism and catabolism of chondrocytes contributes to reduced force absorption ( Chen et al, 2021 ; Tao et al, 2021 ). Collagen II, as one of the most important indexes of anabolism, is the main component of cartilage protein and provides a network structure that can obtain stability from other collagen types and non-collagen proteins and impart tensile strength to articular cartilage ( Miao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

Liang

et al. 2021

Front. Pharmacol.

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Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the in vitro administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1β-induced chondrocyte inflammation response. Moreover, PA reduced IL-1β-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, in vivo experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-κB signaling pathway inhibiting properties of PA on IL-1β-induced chondrocytes could be reversed when integrin αVβ3 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin αVβ3. Thus, PA or integrin αVβ3 might be a promising agent or molecular target for the treatment of OA.

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Section: Discussionmentioning

confidence: 99%

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

Liang

et al. 2021

Front. Pharmacol.

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“…Tao et al used the thermosensitive hydrogel PDLLA-PEG-PDLLA triblock copolymer gel to show good performance in sustained-release EVs. Compared with the direct injection of EVs, it had better long-term effects on the protection of cartilage and delaying the progression of OA [ 79 ].…”

Section: Ev Delivery Biomaterialsmentioning

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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“…Chemical modifications of biopolymers for hydrogel formulation have been extensively reviewed 211 . Biopolymer modifications used for EV retention and delivery for cartilage tissue engineering applications, including the incorporation of biopolymers and carbodiimide crosslinking 212 , 213 , photocrosslinkable methacrylamide-modified gelatin (GelMA) 214 , 215 , modifications to support thiol-ene reactive Michael addition crosslinking 216 , dynamic covalent crosslinking via reversible Diels-Alder reactions 217 , and synthetic thermosensitive triblock copolymers ( Figure 4 ) 218 . The use of various kinds of biomaterials for EV delivery for tissue regeneration in several applications has been thoroughly reviewed 203 , 219 - 224 .…”

Section: Engineering Advanced Therapeutic Strategies In Treating Oa and Cartilage Injurymentioning

confidence: 99%

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

Yin¹,

Ni²,

Witherel³

et al. 2022

Theranostics

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Osteoarthritis (OA) is a prevalent chronic whole-joint disease characterized by low-grade systemic inflammation, degeneration of joint-related tissues such as articular cartilage, and alteration of bone structures that can eventually lead to disability. Emerging evidence has indicated that synovium or articular cartilage-secreted extracellular vesicles (EVs) contribute to OA pathogenesis and physiology, including transporting and enhancing the production of inflammatory mediators and cartilage degrading proteinases. Bioactive components of EVs are known to play a role in OA include microRNA, long non-coding RNA, and proteins. Thus, OA tissues-derived EVs can be used in combination with advanced nanomaterial-based biosensors for the diagnostic assessment of OA progression. Alternatively, mesenchymal stem cell- or platelet-rich plasma-derived EVs (MSC-EVs or PRP-EVs) have high therapeutic value for treating OA, such as suppressing the inflammatory immune microenvironment, which is often enriched by pro-inflammatory immune cells and cytokines that reduce chondrocytes apoptosis. Moreover, those EVs can be modified or incorporated into biomaterials for enhanced targeting and prolonged retention to treat OA effectively. In this review, we explore recently reported OA-related pathological biomarkers from OA joint tissue-derived EVs and discuss the possibility of current biosensors for detecting EVs and EV-related OA biomarkers. We summarize the applications of MSC-EVs and PRP-EVs and discuss their limitations for cartilage regeneration and alleviating OA symptoms. Additionally, we identify advanced therapeutic strategies, including engineered EVs and applying biomaterials to increase the efficacy of EV-based OA therapies. Finally, we provide our perspective on the future of EV-related diagnosis and therapeutic potential for OA treatment.

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Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis

Cited by 92 publications

References 80 publications

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

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

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

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