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Las señales costimuladoras mediadas por el motivo ITAM cooperan con RANKL para la homeostasis ósea
Takako Koga1, Masanori Inui, Kazuya Inoue
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|April 16, 2004
Resumen
Los adaptadores del sistema inmunológico de la subunidad gamma común del receptor Fc (FcRgamma) y la proteína activadora del DNAX (DAP) 12 son cruciales para la salud ósea. Su ausencia perjudica la diferenciación de los osteoclastos, destacando su papel esencial en el mantenimiento de la homeostasis esquelética.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología esquelética Biología esquelética.
- La señalización celular de las células.
Sus antecedentes:
- Las señales costimuladoras son vitales para la activación de las células inmunes, pero su papel en otros sistemas biológicos, como el desarrollo esquelético, es menos comprendido.
- La homeostasis esquelética se basa en un equilibrio entre la formación y la reabsorción ósea, con el receptor activador del ligando NF-kappaB (RANKL) que regula la diferenciación de los osteoclastos.
Objetivo del estudio:
- Para investigar el papel de los adaptadores que albergan el motivo de activación basado en tirosina (ITAM) de los inmunorreceptores en la biología esquelética.
- Aclarar las vías de señalización involucradas en la osteoclastogénesis más allá de la estimulación de RANKL y M-CSF.
Principales métodos:
- Análisis de ratones que carecen de la subunidad gamma común del receptor Fc (FcRgamma) y de la proteína activadora del DNAX (DAP) 12.
- Investigación de la activación de la señalización del calcio en células precursoras de osteoclastos.
- Evaluación de la diferenciación de los osteoclastos y la homeostasis ósea.
Principales resultados:
- Los ratones que carecían de FcRgamma y DAP12 exhibieron osteopetrosis severa debido a la diferenciación deficiente de los osteoclastos.
- Se encontró que FcRgamma y DAP12 se asocian con los inmunorreceptores y activan la señalización del calcio a través de la fosfolipasa Cgamma en los precursores de los osteoclastos.
- Estos hallazgos indican que RANKL y M-CSF por sí solos son insuficientes para la señalización de la osteoclastogénesis.
Conclusiones:
- Las señales costimuladoras dependientes de ITAM, mediadas por FcRgamma y DAP12, son esenciales para la homeostasis ósea.
- Múltiples inmunorreceptores contribuyen al mantenimiento esquelético a través de vías de señalización dependientes de ITAM.
- Este estudio revela un papel novedoso para las señales costimuladoras en la biología esquelética, independiente de las vías previamente conocidas.
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