Project description:Background: Managing early-to-mid-stage knee osteoarthritis (OA) remains an unmet clinical need. Synovitis drives OA progression, but current anti-inflammatory therapies offer limited efficacy. Disrupted fibroblast lineage homeostasis is central in chronic inflammation, and targeting this may attenuate synovitis and pathological synovium-cartilage crosstalk in knee OA. Methods: Synovial single-cell sequencing, clinical histological and transcriptomic data assessed fibroblast lineage changes and similarities between dermal fibroblasts (DFb) and synovial fibroblasts. Labeled DFb injection in rat knees evaluated cell retention. Rat anterior cruciate ligament transection (ACLT) model with intra-articular DFb injection assessed the therapeutic efficacy. Co-cultures characterized DFb paracrine effects on synovial fibroblasts and chondrocytes. Proteomics identified active components in DFb supernatants. Results: OA synovium exhibits disrupted fibroblast lineage homeostasis, marked by a prominent pro-inflammatory phenotype in synovial fibroblasts. DFb show high transcriptomic and morphological similarity to synovial fibroblasts from healthy donors. Post-injection, DFb engrafted within the synovium with more than 3-week retention. Intra-articular DFb injection alleviated synovitis and cartilage degeneration in ACLT-induced OA rats. Co-cultures confirmed DFb alleviated cytokine-induced inflammatory responses in synovial fibroblasts and chondrocytes via paracrine mechanisms, and integrated proteomic/transcriptomic analyses identified apolipoprotein D (APOD) as a potential key mediator of these anti-inflammatory effects. Conclusions: This study validates a novel cell therapy for OA that targets disrupted fibroblast lineage homeostasis in synovitis. By modulating pro-inflammatory synovial fibroblasts and alleviating synovitis through restoring lineage homeostasis, DFb ameliorate OA progression, providing a new theoretical basis and practical approach for OA cell therapy research.
2026-06-24 | GSE327818 | GEO
Project description:Transcriptome Landscape of Mycoplasma Synoviae when exposed to chicken cells
| PRJNA1018222 | ENA
Project description:chicken trachra and spleen transcript profile after Mycoplasma synoviae infection
Project description:Synovial and bone marrow mesenchymal stem cells after intradiscally injection show regenerative effects of nucleus pulposus. Microarray analyses of rats were performed to investigate the closeness of the gene profiles between the nucleus pulposus cells and the synovial or bone marrow mesenchymal stem cells. To investigate interaction between synovial mesenchymal stem cells and nucleus pulposus cells, human synovial mesenchymal stem cells and rat nucleus pulposus cells were co-cultured, and species specific microarray were performed.