The effects of nutrients on stem cell function and regeneration in bone tissue in response to ectopic adipogenesis

Einleitung During aging, adipocytes accumulate in the cavities of long bones by slowly replacing the red, hematopoietic bone marrow. Obesity, caloric restriction (CR), radiation therapy, thiazolidinediones and glucocorticoids accelerate the expansion of bone marrow adipose tissue (BMAT). BMAT secretes adipokines and provides lipids, thereby exerting paracrine and endocrine effects on local stem cells. Excessive BMAT accumulation seems to impair regenerative processes, including hematopoiesis and osteogenesis.

Methoden In mice, a similar pattern of BMAT accumulation occurs. We use a mouse tibia fracture model to investigate how bone regeneration is influenced by aging and nutrient availability. The fracture healing progress is assessed by Micro-CT, gene expression and flow cytometric analyses.

Ergebnisse We find BMAT accumulation changes in response to aging and alterations in the fatty acid composition and gene expression in defined bone compartments. In vitro, we further show changes in the differentiation capacity of defined bone-resident stem cells depending on the cellular microenvironment and the exposure to different nutrients.

Schlussfolgerung In summary, our results demonstrate critical changes in the bone marrow niche as a function of dietary exposure. They highlight nutrient-dependent mechanisms that modulate bone regeneration and BMAT formation as a function of age and diet.

Publication History

Article published online:
04 September 2020