Anti-Hmgb1 polyclonal antibody

Background: Increasing evidence indicates that secretion of high mobility group box 1 protein (HMGB-1) is functionally associated with tendinopathy development. However, the underlying effect and mechanism of extracellular HMGB-1 on tendon cells are unclear. Methods: We tested the effect of exogenous HMGB-1 on cell growth, migration, and inflammatory signaling responses with isolated rat Achilles tendon cells. Also, we studied the role of extracellular HMGB-1, when administrated alone or in combination with mechanical overloading induced by intensive treadmill running (ITR), in stimulating inflammatory effects in tendon tissues. Results: By usingin vitroandin vivomodels, we show for the first time that exogenous HMGB-1 dose-dependently induces inflammatory reactions in tendon cells and tendon tissue. Extracellular HMGB-1 promoted redistribution of HMGB-1 from the nucleus to the cytoplasm, and activated canonical nuclear factor kappa B (NF-kappa B) signaling and mitogen-activated protein kinase (MAPK) signaling. Short-term administration of HMGB-1 induced hyper-cellularity of rat Achilles tendon tissues, accompanied with enhanced immune cell infiltration. Additional ITR to HMGB-1 treatment worsens these responses, and application of HMGB-1 specific inhibitor glycyrrhizin (GL) completely abolishes such inflammatory effects in tendon tissues. Conclusion: Collectively, these results confirm that HMGB-1 plays key roles in the induction of tendinopathy. Our findings improve the understanding of the molecular and cellular mechanisms during tendinopathy development, and provide essential information for potential targeted treatments of tendinopathy.

Osteoclasts are multinucleated bone-resorbing cells derived from monocyte/macrophage progenitor cells. Excessive formation and resorbing activities of osteoclasts are involved in the bone-destructive pathologies of rheumatoid arthritis and osteoporosis. Recently, it has been found that nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor for anti-oxidative stress genes, functions in osteoclastogenesis. Dimethyl fumarate (DMF) is a potent activator of Nrf2 and has been shown to inhibit osteoclastogenesis. Here, we investigated the mechanisms of this inhibition by examining the activation of several signalling pathways during the differentiation of bone marrow-derived macrophages into osteoclasts. DMF inhibited the differentiation of osteoclasts in a dose-dependent manner and suppressed the bone-resorbing activity of osteoclasts. DMF treatment decreased the expression of nuclear factor of activated T-cells cytoplasmic-1, and significantly decreased phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in osteoclasts. We also found that DMF inhibited the extracellular release of high mobility group box 1, associated with an up-regulation of heme oxygenase-1, likely mediated through Nrf2 activation. Our results indicate that DMF inhibits osteoclast differentiation through multiple pathways. (C) 2020 Elsevier Inc. All rights reserved.