Impact of barrier tissue inflammation and physical activity on joint homeostasis in mice.

Objectives: To investigate whether physical activity interferes with joint homeostasis in the presence of distant inflammation originating at barrier tissues such as skin or gut.

Methods: Eight-week-old male C57/Bl6 mice were treated with imiquimod cream on a shaved area of the back skin or with dextran sodium sulphate dissolved in the drinking water to induce psoriasis-like skin or inflammatory bowel disease-like gut inflammation. Afterwards, one group of mice was subjected to a 4-week forced running routine (n = 10 per group). Severity of cutaneous or intestinal inflammation was assessed clinically, by histology and by quantitative PCR. Knees and paws were analysed by micro-CT, histology, immunohistochemistry, second-harmonic generation microscopy and quantitative PCR.

Results: Local induction of inflammation triggered a systemic response with splenomegaly, loss of bone mass and bone marrow changes. Psoriasis- but not inflammatory bowel disease-like inflammation led to synovial lining layer hyperplasia, an increase in infiltrating CD45+ synovial cells, and suppressed entheseal extracellular matrix gene expression levels. Mechanical loading decreased the amount of F4/80+ synovial macrophages in untreated mice only and led to morphological alterations in the collagen fibres of the enthesis.

Conclusion: Systemic inflammation and mechanical loading act independently of each other. The former, originating from distant sites, can trigger mild synovial inflammation in mice, a propensity that may also impact the development of arthritis in patients; the latter has no impact on the severity of systemic inflammation, but independently affects joint homeostasis.