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Las tirosinacinasas Btk y Tec regulan la diferenciación de los osteoclastos mediante la vinculación de las señales
Masahiro Shinohara1, Takako Koga, Kazuo Okamoto
1Department of Cell Signaling, Graduate School, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Cell
|March 11, 2008
Resumen
Los ratones que carecen de tirosina quinasa específica (Btk y Tec) muestran osteopetrosis debido a una función osteoclástica deteriorada. Este estudio descubre un complejo de señalización crucial que involucra a estas quinasas, ofreciendo un potencial objetivo terapéutico para enfermedades óseas.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología ósea Biología ósea Biología ósea Biología ósea
- La señalización celular de las células.
Sus antecedentes:
- Las enfermedades autoinmunes interrumpen la homeostasis ósea, con vínculos con la inmunodeficiencia.
- La diferenciación de los osteoclastos está regulada por las vías de señalización RANK e ITAM.
- La interacción entre estas señales en la osteoclastogénesis sigue sin estar clara.
Objetivo del estudio:
- Investigar el papel de las tirosinacinasas Btk y Tec en la diferenciación de los osteoclastos y la resorción ósea.
- Para dilucidar los mecanismos moleculares que integran la señalización RANK e ITAM en los osteoclastos.
Principales métodos:
- Análisis de la diferenciación de los osteoclastos y la resorción ósea en ratones con deficiencia de Btk/Tec.
- Investigación de la formación de complejos de señalización tras la activación de los receptores RANK e ITAM.
- Inhibición farmacológica de la teccinasa en modelos experimentales de pérdida ósea.
Principales resultados:
- Los ratones que carecían de Btk y Tec mostraron osteopetrosis severa, lo que indica un defecto en la reabsorción ósea.
- La señalización RANK e ITAM convergen para formar un complejo Btk (Tec) / BLNK (SLP-76), activando las señales PLCgamma y Calcio.
- La inhibición de la teccinasa redujo efectivamente la resorción ósea de los osteoclastos en modelos de osteoporosis y destrucción ósea inflamatoria.
Conclusiones:
- Las tirosinacinasas Btk y Tec son esenciales para la diferenciación y la función de los osteoclastos.
- Un nuevo complejo de señalización que involucra a Btk, Tec, BLNK y PLCgamma media la osteoclastogénesis.
- Dirigirse a este complejo de tirosina quinasa presenta una estrategia terapéutica prometedora para las enfermedades óseas.
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