Senescent cell population with ZEB1 transcription factor as its main regulator promotes osteoarthritis in cartilage and meniscus
Authors' conclusion
These single-cell studies identified a senescent pathogenic cell cluster that is present in cartilage and meniscus and has FAP and ZEB1 as main regulators which are novel and promising therapeutic targets for OA-associated pathways in both tissues.
Study context
- Population
- Human healthy and osteoarthritis (OA) knees: articular cartilage and meniscus tissues70,972 cartilage and 78,017 meniscus cells
- Comparison
- Healthy vs OA knee articular cartilage and meniscus
Methodological detailssingle-cell RNA sequencing, immunohistochemistry and RNA-seq validation, gene overexpression and depletion
- Single-cell RNA sequencing
- Immunohistochemistry and RNA-seq validation
- Gene overexpression and depletion
Main finding
As reported in the abstract
- Pathogenic cell subset shared between cartilage and meniscus, expanded in OA, with strong OA and senescence gene signatures
- Subset has critical roles in extracellular matrix (ECM) and tenascin signalling, is the dominant sender of signals to all other clusters and a receiver of TGFβ signalling
- Fibroblast activating protein (FAP) dysregulated in this cluster and promotes ECM degradation
- ZEB1-controlled regulons shared between the pathogenic subset in cartilage and meniscus
- FAP and ZEB1 promote expression of genes contributing to OA pathogenesis, including senescence, in meniscus and cartilage cells
Original publication
Senescent cell population with ZEB1 transcription factor as its main regulator promotes osteoarthritis in cartilage and meniscus. Ann Rheum Dis. Published 23 December 2022. doi:10.
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