Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice

Abstract

Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.

ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway

“…Multiple signaling pathways are involved in the regulation of Atrogin-1 expression. For example, the PI3K/AKT/FOXOs signaling pathway affects Atrogin-1 in muscle atrophy models through the FOXO family by recruiting Atrogin-1 promoter pairs and thus regulating its protein expression ( 28 , 29 ). In the IL-6/JAK/STAT3 signaling pathway, STAT3 phosphorylation activates CCAAT/enhancer binding protein delta, increasing Atrogin-1 expression ( 30 ).…”

Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice

“…Micro-computed tomography (CT) was performed as described in our previous study [ 41 ]. Femurs were fixed in 4% paraformaldehyde for 12 h and transferred to 75% ethanol at 4 °C for analyzing bone microarchitecture by micro-CT at the resolution of 8.96 μm, voltage of 50 kV, and current of 450 mA.…”