Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells

摘要: Skeletal resistance to parathyroid hormone (PTH) is well known the phenomenon in chronic renal failure patient, but detailed mechanism has not been elucidated. In process of analyzing an animal model with low bone turnover, we demonstrated decreased expression PTH receptor (PTHR) accompanying dysfunction this model. present study, focused on accumulation uremic toxins (UTx) blood, and examined whether indoxyl sulfate (IS), a UTx, associated resistance. We established primary osteoblast cultures from mouse calvariae cultured cells presence IS. The intracellular cyclic adenosine 3',5' monophosphate (cAMP) production, PTHR expression, free radical production culture were studied. found that addition IS suppressed PTH-stimulated cAMP system. Free osteoblasts increased depending concentration added. Furthermore, organic anion transporter-3 (OAT-3) mediate cellular uptake was identified culture. These results suggest taken up by via OAT-3 these augments oxidative stress impair function downregulate expression. finding strongly accumulated blood due at least one factors induce skeletal PTH.