Talin1 and Rap1 are critical for osteoclast function.
Mol Cell Biol
; 33(4): 830-44, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23230271
ABSTRACT
To determine talin1's role in osteoclasts, we mated TLN1(fl/fl) mice with those expressing cathepsin K-Cre (CtsK-TLN1) to delete the gene in mature osteoclasts or with lysozyme M-Cre (LysM-TLN1) mice to delete TLN1 in all osteoclast lineage cells. Absence of TLN1 impairs macrophage colony-stimulating factor (M-CSF)-stimulated inside-out integrin activation and cytoskeleton organization in mature osteoclasts. Talin1-deficient precursors normally express osteoclast differentiation markers when exposed to M-CSF and receptor activator of nuclear factor κB (RANK) ligand but attach to substrate and migrate poorly, arresting their development into mature resorptive cells. In keeping with inhibited resorption, CtsK-TLN1 mice exhibit an â¼5-fold increase in bone mass. Osteoclast-specific deletion of Rap1 (CtsK-Rap1), which promotes talin/ß integrin recognition, yields similar osteopetrotic mice. The fact that the osteopetrosis of CtsK-TLN1 and CtsK-Rap1 mice is substantially more severe than that of those lacking αvß3 is likely due to added failed activation of ß1 integrins. In keeping with osteoclast dysfunction, mice in whom talin is deleted late in the course of osteoclastogenesis are substantially protected from ovariectomy-induced osteoporosis and the periarticular osteolysis attending inflammatory arthritis. Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Talina
/
Proteínas rap de Ligação ao GTP
/
Proteínas rap1 de Ligação ao GTP
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos