El rol del inflasoma NLRP3 en la biología de los osteoclastos
NLRP3 inflammasome is involved in many processes of chronic inflammation, and in the maintenance of tissue homeostasis. In bone, NLRP3 is associated with bone loss induced by auto-inflammatory and low-grade chronic inflammatory diseases. In this work, it was shown that bone particle-accelerated oste...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2709 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2709.dir/2709.PDF |
| Aporte de: |
| Sumario: | NLRP3 inflammasome is involved in many processes of chronic inflammation, and in the maintenance of tissue homeostasis. In bone, NLRP3 is associated with bone loss induced by auto-inflammatory and low-grade chronic inflammatory diseases. In this work, it was shown that bone particle-accelerated osteoclastogenesis partially depended on NLRP3,a response that correlated with the activity of this complex. In addition, it was observed that NLRP3 deficiency could lead to the occurrence of compensatory mechanisms activating other inflammasomes. On the other hand, sodium arsenite-induced oxidative stress led to NLRP3-dependent osteoclast differentiation, and NLRP3 was necessary to sustain ROS levels generated by arsenite and RANKL. In an in vivo model, Nlrp3-/-mice displayed less bone loss induced by systemic RANKLinyection compared to wyld type. Moreover, wild type mice produced more IL-1? in bone microenvironment in response to RANKL, an outcome that was dampened by zoledronate administration. Taken together, these data suggest that NLRP3 plays a central role in the maintenance of bone homeostasis, both through IL-1? secretion and by its intrinsic effects on osteoclastogenesis. |
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