Chronic Alcohol Reduces Bone Mass Through Inhibiting Proliferation and Promoting Aging of Endothelial Cells in Type-H Vessels.
Stem Cells Dev
; 31(17-18): 541-554, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35491665
ABSTRACT
Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. This study aimed to determine whether chronic alcohol inhibits type-H vessel-dependent bone formation. Two-month-old mice were fed with 5% (v/v) alcohol liquid diet (28% of calories) or normal liquid diet every day for 2 months. The tibias were isolated and detected with X-ray and microcomputed tomography. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining, respectively. Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of alcohol, including 0 mM (0%), 8.7 mM (0.5%), 52 mM (3%), or 87 mM (5%) alcohol for 12 h. The conditioned medium of the above HUVEC cells was collected to culture human bone marrow-mesenchymal stem cells (BM-MSCs), which were induced to differentiate into osteoblasts in vitro. The alcoholic diet retarded the bone growth and led to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31hiEMCNhi type-H vessel formation through inhibiting proliferation and promoting aging of endothelial cells in mice. Alcohol treatment obviously increased the expression of p16, while significantly decreased the expression of Bmi-1, CDK6, Cyclin D, E2F1, and bone morphogenetic protein (BMP)2 compared with vehicle. Alcohol inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. Alcoholic diet impaired CD31hiEMCNhi type-H vessel formation through inhibiting proliferation and promoting aging of endothelial cells through Bmi-1/p16 signaling, and inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. This study provides a basis for developing a new treatment strategy targeting aging endothelial cells of type-H vessel to prevent alcoholic osteopenia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Óseas Metabólicas
/
Células Endoteliales
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Humans
/
Infant
Idioma:
En
Revista:
Stem Cells Dev
Asunto de la revista:
HEMATOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China