ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
CRISPR-mediated Sox9 activation and RelA inhibition enhance cell therapy for osteoarthritis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- In vitro evaluation of hydroxyapatite, β-tricalcium phosphate, graphene oxide and zinc oxide for osteochondral regeneration under inflammatory conditions.Molecular and cellular biochemistry · 2026Article
- Articular Cartilage Tissue Engineering: Cells, Bioinstructive Scaffolds, Immunological Microenvironment, and Emerging Technologies.Bioengineering (Basel, Switzerland) · 2026Review
- Stem Cell Therapy: Past, Present, and Future Aspects.Biomedicines · 2026Review
- Chondrocytes in fracture healing: A review of chondrocyte journey.Chinese medical journal · 2026Review
- Engineering Approaches to Modify Immunomodulatory Functions of Mesenchymal Stromal Cells (MSCs): Tissue Regeneration and Clinical Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Inflammaging and immunosenescence-driven remodeling of the immune microenvironment in osteoarthritis: mechanisms, immune regulation and immune reprogramming.Frontiers in immunology · 2026Review
- The gut‑bone‑cartilage triad: Microbial regulation of the Wnt/β‑catenin signaling pathway in osteoarthritis joint remodeling (Review).Molecular medicine reports · 2026Review
- Optimizing mesenchymal stem cell therapy for tendon-bone healing: Multifaceted approaches and future directions.World journal of stem cells · 2025Review
- Nanotechnology-driven strategies for gene therapy of arthritis.Materials today. Bio · 2025Review
- From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.Stem cell research & therapy · 2025Review
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- CRISPR/CasRx-mediated RNA knockdown targeting β-catenin and Ihh signaling alleviates osteoarthritis.Genes & diseases · 2025Article
- Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges.Stem cell research & therapy · 2025Review
- ShK-modified UCMSCs Inhibit M1-Like Macrophage Polarization and Alleviate Osteoarthritis Progression via PI3K/Akt Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SOX9: a novel janus-faced regulator in immunity and its promise as a therapeutic target.Frontiers in molecular biosciences · 2025Review
- Optimized Lipid Nanoparticle-Mediated mRNA Co-Delivery of SOX5/SOX9 Enables Synergistic Senescence Reversal for Osteoarthritis Therapy.International journal of nanomedicine · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Osteoarthritis (OA) is a painful and debilitating disease affecting over 500 million people worldwide. Intraarticular injection of mesenchymal stromal cells (MSCs) shows promise for the clinical treatment of OA, but the lack of consistency in MSC preparation and application makes it difficult to further optimize MSC therapy and to properly evaluate the clinical outcomes. In this study, we used Sox9 activation and RelA inhibition, both mediated by the CRISPR-dCas9 technology simultaneously, to engineer MSCs with enhanced chondrogenic potential and downregulated inflammatory responses. We found that both Sox9 and RelA could be fine-tuned to the desired levels, which enhances the chondrogenic and immunomodulatory potentials of the cells. Intraarticular injection of modified cells significantly attenuated cartilage degradation and palliated OA pain compared with the injection of cell culture medium or unmodified cells. Mechanistically, the modified cells promoted the expression of factors beneficial to cartilage integrity, inhibited the production of catabolic enzymes in osteoarthritic joints, and suppressed immune cells. Interestingly, a substantial number of modified cells could survive in the cartilaginous tissues including articular cartilage and meniscus. Together, our results suggest that CRISPR-dCas9-based gene regulation is useful for optimizing MSC therapy for OA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.