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Acoplamiento de la reabsorción ósea y la formación mediante la señalización inversa RANKL
Yuki Ikebuchi1, Shigeki Aoki1, Masashi Honma2
1Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
Nature
|September 7, 2018
Resumen
El activador del receptor osteoblástico del ligando del factor nuclear kappa B (RANKL) se une a RANK vesicular, iniciando la señalización inversa que promueve la formación ósea. Esta vía de señalización inversa de RANKL es crucial para acoplar la reabsorción y la formación ósea.
Área de la Ciencia:
- Biología ósea
- Señalización celular
- Homeostasis del esqueleto
Sus antecedentes:
- El receptor activador del ligando del factor nuclear kappa B (RANK) (RANKL) que se une a RANK inicia la osteoclastogénesis.
- Se conoce el papel de la RANKL osteocítica en la remodelación ósea, pero la función de la RANKL osteoblástica no está clara.
Objetivo del estudio:
- Para aclarar el papel de la RANKL osteoblástica en la formación y remodelación ósea.
- Investigar el mecanismo de la señalización inversa de RANKL en los osteoblastos.
Principales métodos:
- Utilizó ratones mutantes de RANKL ((Pro29Ala) para estudiar el papel del motivo rico en prolina.
- Se investigó la interacción entre el RANK vesicular y el RANKL osteoblástico.
- Se analizó la activación del factor de transcripción 2 relacionado con Runt (Runx2) a través de la señalización inversa de RANKL.
Principales resultados:
- El RANK vesicular secretado por los osteoclastos se une al RANKL osteoblástico.
- Esta unión desencadena la señalización inversa de RANKL, activando Runx2 y promoviendo la formación ósea.
- Una mutación RANKL ((Pro29Ala) interrumpe el motivo rico en prolina, deteriorando la señalización inversa y el acoplamiento óseo.
Conclusiones:
- El RANKL osteoblástico actúa como un receptor de señales para el RANK vesicular, crucial para la formación ósea.
- La señalización inversa de RANKL es esencial para acoplar la reabsorción y la formación ósea.
- La orientación de la señalización inversa de RANKL puede ofrecer estrategias terapéuticas para la pérdida ósea asociada con la inhibición de la osteoclastogénesis.
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