Bone morphogenetic protein 4 is involved in cadmium-associated bone damage.
Toxicol Sci
; 191(2): 201-211, 2023 02 17.
Article
en En
| MEDLINE
| ID: mdl-36453845
ABSTRACT
Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl2) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Cadmio
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Toxicol Sci
Asunto de la revista:
TOXICOLOGIA
Año:
2023
Tipo del documento:
Article