Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility.
Cell Rep
; 27(7): 2050-2062.e6, 2019 05 14.
Article
en En
| MEDLINE
| ID: mdl-31091445
ABSTRACT
Obesity is associated with increased risk for fragility fractures. However, the cellular mechanisms are unknown. Using a translational approach combining RNA sequencing and cellular analyses, we investigated bone marrow stromal stem cells (BM-MSCs) of 54 men divided into lean, overweight, and obese groups on the basis of BMI. Compared with BM-MSCs obtained from lean, obese BM-MSCs exhibited a shift of molecular phenotype toward committed adipocytic progenitors and increased expression of metabolic genes involved in glycolytic and oxidoreductase activity. Interestingly, compared with paired samples of peripheral adipose tissue-derived stromal cells (AT-MSCs), insulin signaling of obese BM-MSCs was enhanced and accompanied by increased abundance of insulin receptor positive (IR+) and leptin receptor positive (LEPR+) cells in BM-MSC cultures. Their hyper-activated metabolic state was accompanied by an accelerated senescence phenotype. Our data provide a plausible explanation for the bone fragility in obesity caused by enhanced insulin signaling leading to accelerated metabolic senescence of BM-MSCs.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Huesos
/
Células de la Médula Ósea
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Diferenciación Celular
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Senescencia Celular
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Células Madre Mesenquimatosas
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Obesidad
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
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Male
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article