Role of canonical Wnt signaling in osteoclast bone resorption
ABSTRACT: It is well known that activation of Wnt/βcatenin signaling in the osteoblast lineage leads to an increase in bone mass increasing osteoblastogenesis and decreasing osteoclastogenesis. However, the role of this pathway on the osteoclast lineage has been understudied. Here, we examined the e...
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/9629 |
| Acceso en línea: | http://hdl.handle.net/10902/9629 |
| Access Level: | acceso abierto |
| Palabra clave: | Hueso βcatenina Osteoclastos CatepsinaK Vía canónica de Wnt Bone βcatenin Osteoclasts CathepsinK Wnt signaling |
| Sumario: | ABSTRACT: It is well known that activation of Wnt/βcatenin signaling in the osteoblast lineage leads to an increase in bone mass increasing osteoblastogenesis and decreasing osteoclastogenesis. However, the role of this pathway on the osteoclast lineage has been understudied. Here, we examined the effects of Wnt/βcatenin signaling in mature osteoclasts by generating mice lacking βcatenin in CathepsinK-expressing cells. These mice developed a severe low-bone-mass phenotype associated with an excessive number of osteoclasts. We found that WNT3A promoted osteoclast apoptosis and therefore, attenuated the number of osteoclasts in vitro. This reveals a cell-autonomous effect of Wnt/βcatenin signaling in the lifespan of osteoclasts. Furthermore, Osteoprotegerin expression was dramatically decreased indicating an additional external activation of osteoclasts. Accordingly, CathepsinK expression was detected in TRAP-negative cells of the inner periosteal layer also expressing Collagen1. Our results indicate that the bone phenotype found in our animals combines a cell-autonomous effect with indirect effects of osteoblastic cells. |
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