ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/056/SRR30464056/SRR30464056_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/055/SRR30464055/SRR30464055_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/054/SRR30464054/SRR30464054_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/062/SRR30464062/SRR30464062_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/063/SRR30464063/SRR30464063_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/058/SRR30464058/SRR30464058_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/057/SRR30464057/SRR30464057_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/061/SRR30464061/SRR30464061_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/060/SRR30464060/SRR30464060_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/059/SRR30464059/SRR30464059_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/057/SRR30464057/SRR30464057_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/063/SRR30464063/SRR30464063_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/053/SRR30464053/SRR30464053_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/060/SRR30464060/SRR30464060_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/054/SRR30464054/SRR30464054_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/052/SRR30464052/SRR30464052_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/053/SRR30464053/SRR30464053_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/052/SRR30464052/SRR30464052_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/062/SRR30464062/SRR30464062_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/061/SRR30464061/SRR30464061_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/056/SRR30464056/SRR30464056_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/059/SRR30464059/SRR30464059_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/058/SRR30464058/SRR30464058_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR304/055/SRR30464055/SRR30464055_1.fastq.gzprimaryOK200GenomicsShenzhen Institute of Advanced Technology, Chinese Academy of Scienceshttps://www.ebi.ac.uk/ena/browser/view/PRJNA1141616Mus musculusOsteoarthritis (OA) is a chronic degenerative joint disease. Currently, OA is incurable. Abnormal activation of canonical Wnt/beta-catenin or Indian hedgehog (Ihh) signaling could lead to OA development and progression. In this study we aimed to determine if targeting beta-catenin and Ihh signaling could yield an effective therapeutic intervention for OA disease. CRISPR/CasRx is a new RNA interference tool that can precisely and efficiently cleave single-strand RNAs. In this study, we screened CRISPR-derived RNA (crRNA) targeting Ctnnb1 and Smo in vitro and selected two optimal crRNAs for each gene. CasRx-mediated Ctnnb1 and Smo knockdown showed high efficiency and specificity with no obvious off-target effects in vitro. We then performed intra-articular injection of selected crRNAs driven by the adeno-associated virus (AAV) into an OA mouse model. Micro-CT, histology and histomorphometrical analysis were conducted to evaluate the CasRx approach on OA treatment. We found that knockdown of Ctnnb1 and Smo decelerates pathological damage in keen joint of the experimental OA mouse model. Our findings suggest that CasRx-mediated Ctnnb1 and Smo knockdown could be a potential strategy for OA treatment.xref:EuropePMC:PMC12033902ENAMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisCRISPR Locus, CRISPR Loci, CRISPR Spacer Sequences, CRISPR Clusters, CRISPR-Cas Loci, RNA, Ribonucleic, CRISPR Sequence, Clustered Regularly Interspaced Short Palindromic Repeat, IHH, Arthritides, ribose nucleic acid, CRISPR Spacer, degenerative arthritis., ribonucleic acids, CRISPR Arrays, CRISPR Array, RNS, CRISPR-Cas, Clusters, PRO2286, Catenin, beta-catenin, Sequences, Xbhh, bhh-a, Osteoarthrosis Deformans, CRISPR Element, CTNNB, osteoarthrosis and allied disorder, Sequence, yeast nucleic acid, Osteoarthritides, Ribonukleinsaeure, CRISPR Elements, Gene Products, pentosenucleic acids, Ribonucleic acids, HHG-2, Spacer, Catnb, ctnnb, beta-Catenin, Osteoarthrosis, Non Polyadenylated, Arrays, CRISPR Spacers, RNA Gene Products, X-hh, Osteoarthritis, Osteoarthroses, ribonucleic acid, Acid, ctnnb1, Element, Arthritis, Elements, BDA1, Non Polyadenylated RNA, Degenerative Arthritides, osteoarthrosis, Non-Polyadenylated, OA, Indian hedgehog protein N-product, Beta-catenin, Ribonucleic Acid, CRISPR Spacer Sequence, hypertrophic arthritis, Locus, beta, CRISPR Sequences, CRISPR Cluster, Indian hedgehog protein C-product, Non-Polyadenylated RNA, CRISPR, CRISPRs, CRISPR-Cas Locus, bhh, degenerative joint disease, OK/SW-cl.35, signalling process, Cluster, HHG2, Degenerative, Loci, Degenerative joint disease, Spacers, Array, Arthrosis, CRISPR Cas Loci, Spacer Sequences, Arthroses, Degenerative Arthritis, Spacer Sequence, single organism signalingfalseMus musculusCRISPR/CasRx-mediated RNA knockdown targeting beta-catenin and Ihh signaling alleviates osteoarthritis2025-09-242024-07-31PRJNA114161610090