Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone Loss

摘要: Our recent animal and human studies revealed that chronic hyponatremia is a previously unrecognized cause of osteoporosis associated with increased osteoclast numbers in rat model the disease syndrome inappropriate antidiuretic hormone secretion (SIADH). We used cellular molecular approaches to demonstrate sustained low extracellular sodium ion concentrations ([Na+]) directly stimulate osteoclastogenesis resorptive activity explore mechanisms underlying this effect. Assays on murine preosteoclastic RAW 264.7 cells primary bone marrow monocytes both indicated lowering medium [Na+] dose-dependently formation activity. Low [Na+], rather than osmolality, triggered these effects. Chronic reduction decreased intracellular calcium without depleting endoplasmic reticulum stores. Moreover, we found uptake radiolabeled ascorbic acid, acid culture mimicked osteoclastogenic effect [Na+]. also detected downstream effects reduced uptake, namely evidence hyponatremia-induced oxidative stress. This was manifested by free oxygen radical accumulation proportional changes protein expression phosphorylation, as Western blot analysis from extracts serum 8-hydroxy-2′-deoxyguanosine levels vivo rats. results therefore reveal novel signaling osteoclasts may serve mobilize stores during prolonged hyponatremia, thereby leading patients SIADH.