The inhibition of bone formation has been suggested to play a central role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). Recently, many studies suggested that there may be another mechanism involved in GIOP besides apoptosis. The aim of this study was to investigate the protective effect of Necrostatin-1 on GIOP rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n=10): controls; GIOP rats; GIOP rats pretreated with alendronate; and GIOP rats pretreated with Necrostatin-1. Their bone mineral density (BMD) and body weight were measured at the beginning and at the end of the experiment. TUNEL assay, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to observe the change of cellular morphology induced by Nec-1. The biochemical analysis and histomorphometric analysis were used to evaluate the change of bone formation by Nec-1. RIP-1, RIP-3 and caspase-8 expression were evaluated by immunohistochemistry. We found more TUNEL positive osteocytes and larger lacunae volume in GIOP rats compared with the control group. However, most of the osteocytes displayed a necrotic morphology and mitochondria lesions under TEM. In contrast to alendronate, Necrostatin-1 significantly elevated the level of bone formation markers, while it had no effect on bone resorption markers. Necrostatin-1 also markedly ameliorated trabecular bone. In addition, Necrostatin-1 significantly weaken the immunoreactivity of RIP-1 in GIOP rats while had no effect on RIP-3 and caspase-8. These data suggest, for the first time, that Necrostatin-1 accelerate bone formation of glucocorticoid-induced osteoporosis in rats.
Keywords: Caspase-8; Glucocorticoid; Necroptosis; Necrostatin-1; Osteoporosis.
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