66 The Effects of Nutrients on Bone Stem Cell Function and Regeneration

Zusammenfassung

In summary, our results show complex changes in the bone marrow niche due to dietary influences. Nutrient-dependent mechanisms influence the differentiation capacity of stem cells and thus modulate fat marrow formation and bone regeneration.

Einleitung

During aging the red hematopoietic bone marrow is slowly replaced by adipocytes. This process starts shortly after birth in the distal part of the skeleton and seems to have physiological functions, as adipocytes secrete adipokines and provide lipids for local stem cells. Obesity and Type 2 Diabetes accelerate the accumulation of fat cells in proximal parts of the skeleton, like femur, hips and vertebrae. The formation of bone marrow adipose tissue during aging and obesity is associated with a decrease in bone density and a higher fracture risk. Paradoxically dietary restriction, also known as caloric restriction, leads to the formation of BMAT, but its effects on bone quality are still unclear. In general, dietary restriction is known for increasing longevity and decreasing the risk for age-related diseases.

Material und Methodik

In order to understand the effects of bone marrow adipose tissue on bone health, we use two different nutritional interventions, high fat diet and dietary restriction, both known to increase fat accumulation in the bone, but with opposing systemic effects. Using a tibia fracture model, we investigate how both interventions affect bone regeneration. Additionally, primary bone stem cells are being isolated using FACS (fluorescence-activated-cell-sorting). In cell culture, the effects of single nutrients, like glucose and fatty acids, and of signaling molecules like insulin, on differentiation are also investigated.

Ergebnisse

The mouse model confirmed the increase of bone marrow adipose tissue during aging and both nutritional interventions. The formation of fat cells is pronounced in certain bone regions and is accompanied by a modified fatty acid composition. The expression of adipogenic and osteogenic marker genes is changed due to the nutritional interventions and are regionally distinct. In bone stem cells, complex influences of glucose, insulin and fatty acids on the differentiation capacity could be shown.

Publication History

Article published online:
24 September 2021