RCANs regulate the convergent roles of NFATc1 in bone homeostasis.
Sci Rep
; 6: 38526, 2016 12 05.
Article
en En
| MEDLINE
| ID: mdl-27917924
ABSTRACT
Activation of calcineurin-dependent nuclear factor of activated T cells c1 (NFATc1) is convergent for normal bone homeostasis. NFATc1 regulates both osteoclastogenesis and osteoblastogenesis. Here we investigated the roles of regulator of calcineurin (RCAN) genes in bone homeostasis. RCANs function as potent physiological inhibitors of calcineurin. Overexpression of RCANs in osteoclast precursor cells attenuated osteoclast differentiation, while their overexpression in osteoblasts enhanced osteoblast differentiation and function. Intriguingly, opposing effects of RCANs in both cell types were shown by blocking activation of the calcineurin-NFATc1 pathway. Moreover, the disruption of RCAN1 or RCAN2 in mice resulted in reduced bone mass, which is associated with strongly increased osteoclast function and mildly reduced osteoblast function. Taken together, RCANs play critical roles in bone homeostasis by regulating both osteoclastogenesis and osteoblastogenesis, and they serve as inhibitors for calcineurin-NFATc1 signaling both in vivo and in vitro.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Huesos
/
Proteínas
/
Péptidos y Proteínas de Señalización Intracelular
/
Factores de Transcripción NFATC
/
Homeostasis
/
Proteínas Musculares
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2016
Tipo del documento:
Article