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Project

Glutamine metabolism in osteocytes during bone homeostasis and pathology

Osteocytes are the most abundant, longest-living cells in the adult skeleton and recent studies have shown that these cells are key regulators of bone mass during homeostasis and pathology. Deeply embedded within the bone matrix, their distant location likely reflects a high sensitivity to nutrient availability to support their function. A central role for cellular metabolism in the functioning of osteogenic cells has recently been shown and glucose appears to fulfill specific metabolic needs. Surprisingly, skeletal cells do not oxidize glucose in the TCA cycle, but rather divert it to the less energetic glycolytic pathway, and I hypothesize that other metabolites are required to meet the high demand for energy, matrix formation and redox homeostasis. As we know from the cancer field, glutamine is a crucial metabolite for tumor cell function, as it complements glucose in energy production, the generation of macromolecules and supports cell defense against oxidative stress, but its role in non-malignant skeletal cells is poorly characterized. Based on my preliminary data, I hypothesize that glutamine metabolism in osteocytes is important for bone homeostasis and osteoporotic bone loss, which I will study using a genetic approach. Moreover, I will explore how glutamine affects osteocyte survival, differentiation and communication to other bone cells. These findings will increase insight in the role of osteocyte metabolism and nutrient availability for skeletal health.

Date:1 Oct 2016 →  30 Sep 2019
Keywords:Glutamine metabolism, osteocytes, bone pathology, bone homeostasis
Disciplines:Animal biology