Emerging Gene-Editing Modalities for Osteoarthritis

Tanikella, Alekya S.; Hardy, Makenna J.; Frahs, Stephanie M.; Cormier, Aidan G.; Gibbons, Kalin; Fitzpatrick, Clare K.; Oxford, Julia Thom

doi:10.3390/ijms21176046

Cited by 18 publications

(13 citation statements)

References 120 publications

(128 reference statements)

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“…CRISPR/Cas9 system has been a promising and powerful gene therapy tool by genome editing 186 . It opens new avenues and possibilities for treating OA.…”

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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“…CRISPR/Cas9 system has been a promising and powerful gene therapy tool by genome editing 186 . It opens new avenues and possibilities for treating OA.…”

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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“…Innovative therapeutic approaches based on genome editing using the CRISPR/Cas9 technique are also being evaluated. The technique has a high potential in regenerative medicine and cell-based applications for cartilage repair [ 106 ].…”

Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies

Valenti

Carbonare

Zipeto

et al. 2021

IJMS

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Autophagy is involved in different degenerative diseases and it may control epigenetic modifications, metabolic processes, stem cells differentiation as well as apoptosis. Autophagy plays a key role in maintaining the homeostasis of cartilage, the tissue produced by chondrocytes; its impairment has been associated to cartilage dysfunctions such as osteoarthritis (OA). Due to their location in a reduced oxygen context, both differentiating and mature chondrocytes are at risk of premature apoptosis, which can be prevented by autophagy. AutophagomiRNAs, which regulate the autophagic process, have been found differentially expressed in OA. AutophagomiRNAs, as well as other regulatory molecules, may also be useful as therapeutic targets. In this review, we describe and discuss the role of autophagy in OA, focusing mainly on the control of autophagomiRNAs in OA pathogenesis and their potential therapeutic applications.

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“…Novel scientific technologies would also aid in the development of tissue engineering ( Figure 2 ). CRISPR/Cas9 system is an advanced genome-editing technique that is able to make gene deletion, correction, and substitution, or other changes at specific sites of the genome ( Tanikella et al, 2020 ). For example, CRISPR/Cas9 has been employed to regulate MMP-13 protein levels and enzymatic activity in human chondrocytes.…”

Section: Summary and Future Outlookmentioning

confidence: 99%

Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends

et al. 2021

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Osteoarthritis (OA) is a leading cause of pain and disability which results in a reduced quality of life. Due to the avascular nature of cartilage, damaged cartilage has a finite capacity for healing or regeneration. To date, conservative management, including physical measures and pharmacological therapy are still the principal choices offered for OA patients. Joint arthroplasties or total replacement surgeries are served as the ultimate therapeutic option to rehabilitate the joint function of patients who withstand severe OA. However, these approaches are mainly to relieve the symptoms of OA, instead of decelerating or reversing the progress of cartilage damage. Disease-modifying osteoarthritis drugs (DMOADs) aiming to modify key structures within the OA joints are in development. Tissue engineering is a promising strategy for repairing cartilage, in which cells, genes, and biomaterials are encompassed. Here, we review the current status of preclinical investigations and clinical translations of tissue engineering in the non-operative treatment of OA. Furthermore, this review provides our perspective on the challenges and future directions of tissue engineering in cartilage regeneration.

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Emerging Gene-Editing Modalities for Osteoarthritis

Cited by 18 publications

References 120 publications

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies

Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends

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