ABSTRACT
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-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-3β (GSK-3β), and β-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-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Subject(s)
Aged , Animals , Female , Humans , Male , Middle Aged , Rats , Bone Density , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 2/complications , Osteoporosis/etiology , Receptor, IGF Type 1/physiology , Signal Transduction , Streptozocin , beta Catenin/physiologyABSTRACT
The aim of this study was observe differences in the immunological distribution of the placental lactogene and IGF-1 receptor on free-chorionic villi, between studied groups and to relate the neonatal diagnosis of PEG with morphometric and immunohystochemical characteristics of the placenta. A total of, twelve placentas from AEG newborn and twelve from PEG newborn were obtained from the Maternity Ward of Temuco, Chile. H&E, Alcian blue and Masson's trichromic stains, as well as Hematoxilyn-PAS. In the immunoperoxidase technique, were used: 1) placental lactogen (polyclonal, dilution 1:200, NCL-PLP, Novocastra) 2) Insuline-1 like growth factor (monoclonal, dilution 1:200, NCL-GHR, Novocastra). Differences between PEG and AEG placentae in the immnunostaing for placental lactogen and IGF-1 receptor in the sincitial throphoblast were not observed.
El objetivo de este estudio fue observar diferencias en la distribución del lactogeno placentario y receptor del factor de crecimiento similar a la insulina, entre placentas de recién nacidos normales para la edad gestacional AEG y pequeños para la edad gestacional PEG. Un total de 12 placentas de recién nacidos AEG y 12 PEG obtenidas de la maternidad del Hospital de Temuco, Chile fueron procesadas con técnicas histológicas H&E, azul de Alcián y un método de tinción tricrómico. La técnica de inmunoperoxidasa utilizada fue: 1) lactogeno placentario (pohclonal, dilución 1:200, NCL-PLP, Novocastra) 2) Factor de crecimiento similar a la insulina (monoclonal, dilución 1:200, NCL-GHR, Novocastra). No se observaron diferencias en la distribución de lactogeno placentario ni factor de crecimiento similar a la insulina entre las placentas provenientes de recién nacidos pequeños para la edad gestacional y adecuados para la edad gestacional.
Subject(s)
Humans , Infant, Newborn , Placental Lactogen/physiology , Receptor, IGF Type 1/physiology , Chorionic Villi/anatomy & histology , Chorionic Villi/physiology , Infant, Small for Gestational AgeABSTRACT
O crescimento, principal característica da infância e da adolescência, apresenta padrão semelhante na maioria dos indivíduos. A herança genética e os componentes do eixo GH-IGF são os fatores que diretamente influenciam esse processo. O GH, produzido na hipófise, exerce sua ação sobre o crescimento mediante regulação do sistema IGF. Os IGFs (IGF-1 e IGF-2) são fatores de crescimento produzidos na maioria dos órgãos e tecidos do organismo, possuindo ações autócrinas, parácrinas e endócrinas sobre o metabolismo intermediário, proliferação, crescimento e diferenciação celular. Associam-se com elevado grau de especificidade e de afinidade à família de seis proteínas carreadoras, denominadas IGFBPs (IGFBP-1 a -6), as quais modulam suas bioati-vidades. A maioria das ações conhecidas dos IGFs é exercida mediante sua ligação com o receptor tipo 1 (IGF-1R). Neste artigo será revisada a composição e a regulação do eixo GH-sistema IGF, assim como a participação de cada um dos seus diferentes componentes no processo de regulação do crescimento humano.
Growth, the main characteristic of childhood and adolescence, has a similar pattern in the majority of the individuals. Genetic background and GH-IGF axis are the factors that directly influence this process. Pituitary GH acts on growth mainly through the regulation of IGF system. The IGFs (IGF-1 and IGF-2) are growth factors produced in the majority of the organs and body tissues. They have autocrine, paracrine and endocrine actions on metabolism and cell proliferation, growth and differentiation. The IGFs bind with high specificity and affinity to a family of 6 binding proteins, called IGFBPs (1 to 6) that modulate their bioactivity. Most of the known IGF actions are mediated via IGF type 1 receptor (IGF1R). In this article we are going to review the composition and regulation of the GH-IGF axis and the role of each component in the regulation of the growth process.