Evaluation of serum myostatin and sclerostin levels in chronic spinal cord injured patients.

STUDY DESIGN: Case-control study. OBJECTIVES: To assess serum myostatin levels, bone mineral density (BMD), appendicular skeletal muscle mass (ASMM) and serum sclerostin levels in chronic spinal cord injured (SCI) patients and healthy controls. SETTING: SCI centre in Italy. METHODS: Blood samples, whole-body bioelectrical impedance analysis and BMD measurement with the ultrasound technique at the calcaneus level were taken from patients suffering from chronic SCI (both motor complete and incomplete) and healthy control subjects. RESULTS: A total of 28 SCI patients and 15 healthy controls were enrolled. Serum myostatin levels were statistically higher (P<0.01) in SCI patients compared with healthy controls. Similar results were found comparing both the motor complete and the motor incomplete SCI subgroups to healthy controls. Serum sclerostin was significantly higher in patients with SCI compared with healthy controls (P<0.01). BMD, stiffness and mean T-score values in SCI patients were significantly lower than those in healthy controls. Serum myostatin concentrations in the motor complete SCI subgroups correlated only with serum sclerostin levels (r(2)=0.42; P=0.001) and ASMM (r(2)=0.70; P=0.002) but not in healthy controls. DISCUSSION: Serum myostatin and serum sclerostin are significantly higher in chronic SCI patients compared with healthy controls. They are potential biomarkers of muscle and bone modifications after SCI. This is the first study reporting an increase in serum myostatin in patients suffering from chronic SCI and a correlation with ASMM.

Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways.

CONTEXT: Recently, vitamin D (VitD) has been recognized as increasingly importance in many cellular functions of several tissues and organs other than bone. In particular, VitD showed important beneficial effects in the cardiovascular system. Although the relationship among VitD, endothelium, and cardiovascular disease is well established, little is known about the antioxidant effect of VitD. OBJECTIVE: Our objective was to study the intracellular pathways activated by VitD in cultured human umbilical vein endothelial cells undergoing oxidative stress. DESIGN: Nitric oxide production, cell viability, reactive oxygen species, the mitochondrial permeability transition pore, membrane potential, and caspase-3 activity were measured during oxidative stress induced by administration of 200 µM hydrogen peroxide for 20 minutes. Experiments were repeated in the presence of specific vitamin D receptor ligand ZK191784. RESULTS: Pretreatment with VitD alone or in combination with ZK191784 is able to reduce the apoptosis-related gene expression, involving both intrinsic and extrinsic pathways. At the same time, it has been shown the activation of pro-autophagic beclin 1 and the phosphorylation of ERK1/2 and Akt, indicating a modulation between apoptosis and autophagy. Moreover, VitD alone or in combination with ZK191784 is able to prevent the loss of mitochondrial potential and the consequent cytochrome C release and caspase activation. CONCLUSIONS: The present study shows that VitD may prevent endothelial cell death through modulation of the interplay between apoptosis and autophagy. This effect is obtained by inhibiting superoxide anion generation, maintaining mitochondria function and cell viability, activating survival kinases, and inducing NO production.