V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption.
Int J Biochem Cell Biol
; 44(9): 1422-35, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22652318
ABSTRACT
The vacuolar-type H(+)-ATPase (V-ATPase) proton pump is a macromolecular complex composed of at least 14 subunits organized into two functional domains, V(1) and V(0). The complex is located on the ruffled border plasma membrane of bone-resorbing osteoclasts, mediating extracellular acidification for bone demineralization during bone resorption. Genetic studies from mice to man implicate a critical role for V-ATPase subunits in osteoclast-related diseases including osteopetrosis and osteoporosis. Thus, the V-ATPase complex is a potential molecular target for the development of novel anti-resorptive agents useful for the treatment of osteolytic diseases. Here, we review the current structure and function of V-ATPase subunits, emphasizing their exquisite roles in osteoclastic function. In addition, we compare several distinct classes of V-ATPase inhibitors with specific inhibitory effects on osteoclasts. Understanding the structure-function relationship of the osteoclast V-ATPase may lead to the development of osteoclast-specific V-ATPase inhibitors that may serve as alternative therapies for the treatment of osteolytic diseases.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Resorción Ósea
/
ATPasas de Translocación de Protón Vacuolares
/
Inhibidores Enzimáticos
Idioma:
En
Revista:
Int J Biochem Cell Biol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Australia