Anabolic actions of Notch on mature bone.
Proc Natl Acad Sci U S A
; 113(15): E2152-61, 2016 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-27036007
ABSTRACT
Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response.
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Base de dados:
MEDLINE
Assunto principal:
Osso e Ossos
/
Receptores Notch
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article