Disentangling the detrimental effects of local from systemic adipose tissue dysfunction on articular cartilage in the knee.

Objective: Obesity increases osteoarthritis (OA) risk due to adipose tissue dysfunction with associated metabolic syndrome and excess weight. Lipodystrophy syndromes exhibit systemic metabolic and inflammatory abnormalities similar to obesity without biomechanical overloading. Here, we used lipodystrophy mouse models to investigate the effects of systemic versus intra-articular adipose tissue dysfunction on the knee.

Taxonomy of fibroblasts and progenitors in the synovial joint at single-cell resolution.

Objectives: Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and + connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.

Methods: To discriminate between -lineage cells deriving from the embryonic joint interzone and other -expressing fibroblasts and progenitors, adult mice were used and cartilage injury was induced to activate progenitors.

Targeting the IL-6-Yap-Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis.

Objective: We aimed to understand the role of the transcriptional co-factor Yes-associated protein (Yap) in the molecular pathway underpinning the pathogenic transformation of synovial fibroblasts (SF) in rheumatoid arthritis (RA) to become invasive and cause joint destruction.

Methods: Synovium from patients with RA and mice with antigen-induced arthritis (AIA) was analysed by immunostaining and qRT-PCR. SF were targeted using and mice, crossed with fluorescent reporters for cell tracing and mice for conditional ablation.