Endocrine Abstracts

Hyponatraemia represents an independent risk factor for osteoporosis and fractures, affecting both bone density and quality. A direct stimulation of osteoclastogenesis and bone resorption in the presence of reduced extracellular sodium concentrations ([Na+]) has been shown, but, to date, the effects of reduced [Na+] on osteoblasts have not been elucidated. This study investigated the effects of a chronic reduction of extracellular [Na+], independently of osmotic stress, on human mesenchymal stromal cells (hMSC) from bone marrow, the common progenitor for osteoblasts and adipocytes. As regards hMSC homeostasis, we found a significant inhibition of adhesion and viability, but no alteration of their surface antigen profile and immuno-modulatory properties. Low extracellular [Na+] were able to modulate the osteoblastic production of factors (MCP-1 and CXCL-12) that stimulate osteoclast recruitment and bone resorption. Next, we tested whether chronic hyponatremia was able to alter the cellular commitment of hMSC. We found that hMSC maintained their ability to commit toward the osteogenic and the adipogenic phenotypes, as demonstrated by the unaltered gene expression of specific differentiation markers. However, the dose-dependent increase in the number of adipocytes as a function of reduced [Na+], observed by Oil-Red-O staining, suggested a preferential commitment toward the adipogenic phenotype at the expense of osteogenesis. This observation was further supported by the amplified inhibitory effect on the expression of osteoblastic markers exerted by adipocyte-conditioned media in low [Na+] conditions. Finally, the analysis of cytoskeleton by immunofluorescent microscopy showed that low [Na+] was associated with disruption of tubulin organization in hMSC-derived osteoblasts, thus suggesting a negative effect on bone quality. These findings add new evidence that hyponatremia should be carefully taken into account by clinicians because of its negative effects on bone, in addition to the known neurological effects, and indicate for the first time that impaired osteogenesis may be involved.