Roles of Del-1 in effects of hyponatremia on muscle and bone in mice.
This study identifies Del-1 as a myokine that may link muscle health to bone density in the context of hyponatremia in mice.
Where it sits
this study against the rest of the desmopressin corpusSummary and findings
This study investigated the effects of hyponatremia on muscle and bone in mice, focusing on the myokine Del-1. Mice were treated with 1-desamino-8-D-arginine vasopressin (dDAVP) and furosemide for 8 weeks. The results indicated a down-regulation of Del-1 expression in muscle tissues and a correlation with bone density metrics.
Abstract
Hyponatremia induces both osteoporosis and sarcopenia. Although interactions between muscle and bone have been extensively examined, the myokines affecting bone in the hyponatremic state remain unclear. Therefore, we herein investigated myokines linking muscle to bone in the hyponatremic state using mice treated with 1-desamino-8-D-arginine vasopressin (dDAVP) and furosemide for 8 weeks. An RNA-sequencing analysis showed that the expression of developmental endothelial locus-1 (Del-1), a humoral factor, was down-regulated by hyponatremia in the gastrocnemius muscles of mice. dDAVP and furosemide significantly reduced Del-1 expression in the gastrocnemius and soleus muscles as well as circulating Del-1 levels in mice. Low sodium concentrations also decreased Del-1 expression in mouse myoblasts and myotubes. Del-1 significantly suppressed osteoclast formation in mouse bone marrow cells. A simple regression analysis revealed that serum Del-1 levels and Del-1 mRNA levels in the gastrocnemius muscle were positively correlated with trabecular bone volume fraction and cortical bone mineral density in mice. In conclusion, we herein identified Del-1 as a myokine linking muscle to bone in hyponatremia. The present results suggest that decreased expression of Del-1 in skeletal muscles might contribute to hyponatremia-induced bone loss in mice.
Background
Hyponatremia is known to induce osteoporosis and sarcopenia, but the specific myokines that affect bone in this condition remain unclear. Prior research has established a connection between muscle and bone health, yet the role of Del-1 in this interaction has not been thoroughly investigated. This study aims to elucidate the relationship between muscle-derived Del-1 and bone health in the context of hyponatremia.
Methods
The study utilized a mouse model with a sample size that is not specified in the abstract. Mice were treated with 1-desamino-8-D-arginine vasopressin (dDAVP) and furosemide for a duration of 8 weeks. The primary outcome measures included Del-1 expression levels in muscle tissues and correlations with bone density metrics.
Results
Del-1 expression was significantly down-regulated in the gastrocnemius and soleus muscles due to hyponatremia. Furthermore, a simple regression analysis revealed a positive correlation between serum Del-1 levels and trabecular bone volume fraction, as well as cortical bone mineral density.
Interpretation
The findings suggest that decreased Del-1 expression in skeletal muscles may contribute to bone loss associated with hyponatremia. While the results are statistically significant, the clinical relevance remains uncertain without human data. The study's reliance on mouse models introduces confounding factors that may limit the applicability of the results to human health.
Key findings
- Del-1 expression was down-regulated by hyponatremia in the gastrocnemius muscles of mice.
- dDAVP and furosemide significantly reduced Del-1 expression in the gastrocnemius and soleus muscles as well as circulating Del-1 levels in mice.
- Serum Del-1 levels and Del-1 mRNA levels in the gastrocnemius muscle were positively correlated with trabecular bone volume fraction and cortical bone mineral density in mice.
Limitations
- Not reported in abstract.
- Mouse model may not fully represent human physiology.
- Short duration of 8 weeks may not capture long-term effects.
- Industry funding not disclosed in abstract.