RESUMEN
Histone deacetylases (HDACs) are negative regulators of transcription and have been shown to regulate specific changes in gene expression. In vertebrates, eighteen HDACs have thus far been identified and subdivided into four classes (I-IV). Key roles for several HDACs in bone development and biology have been elucidated through in vitro and in vivo models. By comparison, there is a paucity of data on the roles of individual HDACs in osteoclast formation and function. In this study, we investigated the gene expression patterns and the effects of suppressing individual class II (Hdac4, 5, 6, 9, and 10) and class IV (Hdac11) HDACs during osteoclast differentiation. We demonstrated that HDAC class II and IV members are differentially expressed during osteoclast differentiation. Additionally, individual shRNA-mediated suppression of Hdac4, 5, 9, 10 and 11 expression resulted in increased multinucleated osteoclast size and demineralization activity, with little to no change in the overall number of multinucleated osteoclasts formed compared with control shRNA-treated cells. We also detected increased expression of genes highly expressed in osteoclasts, including c-Fos, Nfatc1, Dc-stamp and Cathepsin K. These observations indicate that HDACs cooperatively regulate shared targets in a non-redundant manner.
Asunto(s)
Diferenciación Celular/fisiología , Histona Desacetilasas/fisiología , Osteoclastos/citología , Osteogénesis/fisiología , Animales , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
We studied the impacts of exposure to ultra-low volume (ULV) applications of resmethrin (Scourge) on monarch butterfly (Danaus plexippus) larvae and adults. In a series of 3 experiments, we measured short- and long-term survival of monarch larvae and adults, and the impacts of consuming previously exposed host plants on monarch larvae. We measured efficacy during all experiments with caged sentinel mosquitoes, and during Experiments 1 and 2 with pretreatment, treatment, and posttreatment measurements of mosquito abundance in CO2 traps. Downwind monarch larval and adult mortality were higher than upwind or control mortality up to 120 m, but not 170 m, from the spray path. In 1 experiment, monarchs exposed to spray as larvae developed into smaller adults, suggesting sublethal impacts. Milkweed host plants sprayed 1, but not 2 or 4 days previously, resulted in increased monarch larval mortality. Sentinel mosquito mortality was generally high, and CO2 traps revealed substantially lower mosquito abundance immediately after the treatment (>90% reduction) but <20% reduction 24 h after treatment. Our results suggest that ULV resmethrin applications will impact lepidopteran larvae and adults that are directly exposed to the spray but that generalizations about other nontarget taxa will require additional research. The magnitude of population-level impacts on monarchs will depend on the proportion of the population that is exposed.