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Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling

ABSTRACT: To investigate skin aging is an important driver of experimental osteoarthritis(OA) progression in mice via enhanced IL-36 receptor (IL-36R) signaling. The supernatants from the co-culture of UV-aged mouse primary keratinocytes with synovial fibroblasts were collected to induce mouse primary articular chondrocytes (CCs) to become aging SNL CCs. On this basis, Spesolimab (100ng/ml) was added to culture aging SNL CCs to study the drug's effect on OA. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 groups: control CCs, aging SNL CCs, aging SNL CCs+Spesolimab.

ORGANISM(S): Mus musculus

PROVIDER: GSE264103 | GEO | 2024/05/01

REPOSITORIES: GEO

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Project description:Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. The underlying pathogenesis of OA is yet to be fully elucidated with no OA specific biomarkers in clinical use. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) allow identification of the global metabolome and proteome respectively. During this study, ex-vivo equine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1H NMR metabolic analysis with media samples also undergoing MS proteomic analysis. Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six metabolites were identified as being differentially abundant between control and treatment groups for 1-2 day, 3-5 day and 6-8 day time points respectively. Culture media proteomics identified 154, 138 and 72 proteins differentially abundant, with > 2 fold change, between control and treatment groups for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. This is the first study to use a multi ‘omics’ approach to simultaneously investigate the metabolomic profile of ex-vivo cartilage and metabolomic/proteomic profiles of culture media using the TNF-α/IL-1β ex-vivo OA cartilage model. This study has identified a panel of metabolites, proteins and extracellular matrix derived neopeptides which are differentially abundant during an early phase of the OA model which may provide further information on underlying disease pathogenesis, allow potential translation for clinical markers and possible novel therapeutic targets.

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Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling

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