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.