Anti-Okadaic Acid polyclonal antibody

Receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis is believed to play a critical role in osteolytic diseases including peri-prosthetic osteolysis (PPO), the primary reason for implant failure and revision surgery. In this study, we observed that protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, was highly expressed in human periprosthetic interface membranes with aseptic loosening and in a murine osteolysis model induced by titanium particle irritation. PP2A inhibition effectively alleviated titanium particle-induced bone destruction at osteolytic sites. In addition, PP2A downregulation significantly decreased osteoclast numbers and RANKL expression, compared with in animals treated with only titanium. Mechanistically, a PP2A selective inhibitor or PP2A siRNA suppressed osteoclastogenesis and alleviated osteoclastic resorption by inhibiting the RANKL-induced nuclear factor-KB and c-Jun N-terminal kinase signaling pathways. Downstream NFATcl and c-Fos expression were also substantially suppressed by PP2A inhibition or knockdown. Our findings support the importance of PP2A during osteoclastogenesis, identifying PP2A as a novel target for treating particle-induced or other osteoclast-mediated bone resorption diseases. Statement of significance Excessive osteoclast activation disrupts bone homeostasis and leads to osteoclast-mediated bone resorption diseases, such as pen-prosthetic osteolysis, regarded as the primary reason for implant failure and revision surgery. Here, we firstly demonstrated protein phosphatase 2A (PP2A), a major serinethreonine phosphatase, was highly expressed in human periprosthetic interface membranes with aseptic loosening and murine osteolysis model. Moreover, PP2A inhibition effectively alleviated titanium particle-induced bone destruction and decreased osteoclast numbers. Meanwhile, a PP2A selective inhibitor or PP2A siRNA suppressed osteoclastogenesis and alleviated osteoclastic resorption by inhibiting the nuclear factor-kappa B and c-Jun N-terminal kinase signaling pathways. Thus, PP2A is involved in osteoclastogenesis and could be a promising target for regulating bone homeostasis and osteolytic responses. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Many benthic dinoflagellates are known or suspected producers of lipophilic polyether phycotoxins, particularly in tropical and subtropical coastal zones. These toxins are responsible for diverse intoxication events of marine fauna and human consumers of seafood, but most notably in humans, they cause toxin syndromes known as diarrhetic shellfish poisoning (DSP) and ciguatera fish poisoning (CFP). This has led to enhanced, but still insufficient, efforts to describe benthic dinoflagellate taxa using morphological and molecular approaches. For example, recently published information on epibenthic dinoflagellates from Mexican coastal waters includes about 45 species from 15 genera, but many have only been tentatively identified to the species level, with fewer still confirmed by molecular criteria. This review on the biodiversity and biogeography of known or putatively toxigenic benthic species in Latin America, restricts the geographical scope to the neritic zones of the North and South American continents, including adjacent islands and coral reefs. The focus is on species from subtropical and tropical waters, primarily within the genera Prorocentrum, Gambierdiscus/Fukuyoa, Coolie, Ostreopsis and Amphidinium. The state of knowledge on reported taxa in these waters is inadequate and time-series data are generally lacking for the prediction of regime shift and global change effects. Details of their respective toxigenicity and toxin composition have only recently been explored in a few locations. Nevertheless, by describing the specific ecosystem habitats for toxigenic benthic dinoflagellates, and by comparing those among the three key regions - the Gulf of Mexico, Caribbean Sea and the subtropical and tropical Pacific coast, insights for further risk assessment of the global spreading of toxic benthic species is generated for the management of their effects in Latin America.