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IGF-1R/?-catenin signaling axis is involved in type 2 diabetic osteoporosis.

ABSTRACT: Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/?-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ ?-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3? (GSK-3?), and ?-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3?, and ?-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/?-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.

SUBMITTER: Zhang ZD

PROVIDER: S-EPMC6751485 | biostudies-literature | 2019 Oct.

REPOSITORIES: biostudies-literature

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IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis.

Zhang Zhi-Da ZD Ren Hui H Wang Wei-Xi WX Shen Geng-Yang GY Huang Jin-Jing JJ Zhan Mei-Qi MQ Tang Jing-Jing JJ Yu Xiang X Zhang Yu-Zhuo YZ Liang De Yang Zhi-Dong ZD Jiang Xiao-Bing XB

Journal of Zhejiang University. Science. B 20191001 10

Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high- ...[more]

PMID: 31489803

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IGF-1R/?-catenin signaling axis is involved in type 2 diabetic osteoporosis.

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IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis.

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