Tipo de Articulo: Artículos Originales

Titulo: Mediadores intercelulares de la regulacin de la remodelacin sea en un modelo experimental de patologa renal

Title: Intercellular mediators in bone remodeling regulation in the experimental renal pathology

Actual. Osteol 15(3):180:191, 2019

Autor(es): Sergey Pavlov, Nataliia Babenko, Marina Kumetchko, Olga Litvinova, Natalia Semko, Olga Pavlova


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Las enfermedades metablicas seas se caracterizan por un desequilibrio en el proceso de remodelacin sea en los que participan mediadores tales como receptor del activador del factor nuclear kappa β (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, frecuentemente empleados en el tratamiento de la enfermedad renal crnica, exacerban este desequilibrio. En la enfermedad esclertica renal, las molculas de adhesin celular P-selectina and galectina-3 tienen un rol fundamental.

El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelacin sea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crnica con tratamiento glucocorticoideo.

Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crnica con afeccin de la remodelacin sea (ERC); animales con afeccin de la remodelacin sea expuestos a glucocorticoides (GC); enfermedad renal crnica con afeccin de la remodelacin sea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioqumicamente, histolgicamente y por medicin de la densidad sea. RANKL, OPG, P-selectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno anlisis.

En los 3 grupos experimentales la densidad sea se evidenci reducida y los niveles sricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmtica en GC y ERC+GC se encontr reducida y aumentada en los animales ERC, en comparacin con los animales controles. La concentracin srica de P-selectina srica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmticos de los animales intactos.

El avance del conocimiento sobre la re gulacin de la remodelacin sea a travs de la interaccin de mediadores sistmicos, en un futuro, puede conducir al desarrollo de nuevas estrategias teraputicas para la prevencin de la osteoporosis en pacientes con enfermedad renal crnica.



Palabras clave: remodelacin sea, enfermedad renal crnica, glucocorticoides; cito-quinas.

Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappaβreceptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG).

The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids.

Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzyme- linked immunoassay was used to measure intercellular mediator levels in the serum.

The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group.

In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future.





Keywords: bone remodeling, renal insuf!ciency, chronic, glucocorticoids, cytokines.

Propietario: Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM)
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