Background Recent studies have demonstrated that there is an inverse relationship between lymphatic egress and inflammatory arthritis in affected joints. As a model, TNF-transgenic (TNF-Tg) mice develop advanced arthritis following draining lymph node collapse, and loss of lymphatic contractions downstream of inflamed joints. As it is unknown if these lymphatic deficits are reversible, we tested the hypothesis that anti-TNF therapy reduces advanced inflammatory-erosive arthritis, associated with restoration of lymphatic contractions, repair of damaged lymphatic vessels, and evidence of increased monocyte egress. Methods TNF-Tg mice with advanced arthritis and collapsed popliteal lymph nodes (PLN) were treated with anti-TNF monoclonal antibody (10 mg/kg weekly) or placebo for 6-weeks, and effects on knee synovitis, efferent lymphatic vessel ultrastructure and function, and PLN cellularity were assessed by ultrasound, histology, transmission electron microscopy (TEM), near infrared indocyanine green (NIR-ICG) imaging, and flow cytometry, respectively. Results Anti-TNF therapy significantly decreased synovitis ~5-fold (p<0.05 vs. placebo), restored lymphatic contractions, and significantly increased PLN monocytes/macrophages ~2-fold (p<0.05 vs. placebo). TEM demonstrated large activated macrophages attached to damaged lymphatic endothelium in mice with early arthritis, extensively damaged lymphatic vessels in placebo-treated mice with advanced arthritis, and rolling leukocytes in repaired lymphatic vessels in mice responsive to anti-TNF therapy. Conclusion These findings support the concept that anti-TNF therapy ameliorates inflammatory-erosive arthritis, in part, via restoration of lymphatic vessel contractions and potential enhancement of inflammatory cell egress.

Background:The Warburg effect in cancer is manifested by increased glycolysis and decreased respiration. Our goal was to determine how mitochondria are suppressed in osteosarcoma (OS). Results: OS cells showing the Warburg effect have markers of the mitochondrial permeability transition (MPT). Conclusion:MPT plays a possible role in suppression of mitochondrial function in OS. Significance: Our data implicate the MPT in metabolic reprogramming in cancer.

Our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates cross-talk between the actin and microtubule cytoskeleton and maintains ID integrity and cardiomyocyte homeostasis in heart disease.

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