IGF-1R/β-catenin signaling axis is implicated in streptozotocin exacerbating bone impairment in ovariectomized rats

Abstract

Objective The aim of this study was to investigate the role of the insulin-like growth factor-1 receptor (IGF-1R)/β-catenin signaling axis in bone impairment induced by hyperglycemia in ovariectomized rats. Methods Rats were divided into four groups. The sham group received sham operation and a single intraperitoneal administration of vehicle. The ovariectomy (OVX) group was subjected to bilateral OVX and vehicle injection. The streptozotocin (STZ) group received sham operation and a single STZ injection to induce hyperglycemia. The OVX + STZ group received bilateral OVX and a single STZ injection. Dual-energy X-ray absorptiometry measurement, bone biomechanics test, micro-computed tomography scan, and hematoxylin–eosin staining were performed to evaluate bone alteration in this model. The expression of relevant signals including IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin were examined by quantitative real-time polymerase chain reaction and western blot. Results The OVX, STZ, and OVX + STZ groups induced bone loss, attenuated bone strength, and impaired microarchitecture compared with the sham group, respectively. Compared with OVX, more serious bone damage was found in the OVX + STZ group, which showed enhanced phosphorylation of IGF-1R, GSK-3β, and β-catenin. Conclusion OVX plus STZ induced more serious bone impairment than OVX alone, which involves the IGF-1R/β-catenin signaling axis in the pathogenesis. This may provide a potential target for treatment of postmenopausal diabetic osteoporosis.