Dynamic network biomarker identifies cdkn1a-mediated bone mineralization in the triggering phase of osteoporosis.
Exp Mol Med
; 55(1): 81-94, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36599933
ABSTRACT
The identification of predictive markers to determine the triggering phase prior to the onset of osteoporosis is essential to mitigate further irrevocable deterioration. To determine the early warning signs before osteoporosis, we used the dynamic network biomarker (DNB) approach to analyze time-series gene expression data in a zebrafish osteoporosis model, which revealed that cyclin-dependent kinase inhibitor 1 A (cdkn1a) is a core DNB. We found that cdkn1a negatively regulates osteogenesis, as evidenced by loss-of-function and gain-of-function studies. Specifically, CRISPR/Cas9-mediated cdkn1a knockout in zebrafish significantly altered skeletal development and increased bone mineralization, whereas inducible cdkn1a expression significantly contributed to osteoclast differentiation. We also found several mechanistic clues that cdkn1a participates in osteoclast differentiation by regulating its upstream signaling cascades. To summarize, in this study, we provided new insights into the dynamic nature of osteoporosis and identified cdkn1a as an early-warning signal of osteoporosis onset.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteoporosis
/
Calcificación Fisiológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Exp Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2023
Tipo del documento:
Article