Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions

Abstract

Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions.

Metabolic Switch Under Glucose Deprivation Leading to Discovery of NR2F1 as a Stimulus of Osteoblast Differentiation

“…(15)(16)(17)(18)(19) More recently, glucose transporter 1 (GLUT1) has been shown to be a major transporter in primary osteoblast cultures that can modulate posttranslational modification of Runx2 by suppressing adenosine 5 0monophosphate kinase and blocking ubiquitination of Runx2. (14)(15)(16)(17)(18)(19)(20) In the current study, we implemented an in vitro "glucose-stressed metabolic model" mimicking a glucosedeficient microenvironment encountered during cell transplantation in vivo. Metabolic profiles of glucose-deprived cells and glucose-supplemented stem cells differentiated in an osteogenic differentiation medium were then compared.…”

“…(15)(16)(17)(18)(19) These new insights have prompted the development of strategies aiming to discover novel genes that can simultaneously improve cell viability and osteogenic differentiation under ischemic conditions, thereby overcoming this major roadblock. (19)(20)(21) Although glucose uptake and aerobic glycolysis have been reported to play important roles in bone formation, (17)(18)(19)(20) reports on changes of metabolites in a glucose-deprived osteogenic microenvironment are lacking.…”

Endocrinal metabolic regulation on the skeletal system in post-menopausal women

“…This mechanism enhanced the differentiation and activation of osteoclasts. Despite an increase in bone density in osteoporotic mice, the reduced bone mass was observed in healthy mice upon the blockage of glycolysis (Donat et al, 2021). The reason behind such observation might be due to the adverse effect of glycolysis blockage on new bone forming osteoblasts and osteocytes.…”

Amino acid metabolism in primary bone sarcomas

“…Specialized osteoblast cells needed to build bone require the generation of high levels of ATP ( 23 ). Osteoblasts express 3 glucose transporters (GLUT1, GLUT3, and GLUT4) to facilitate glucose uptake ( 37 – 39 ). In vitro studies, including metabolic tracing with murine calvarial cells, showed that osteoblast differentiation under aerobic conditions increases glucose consumption and lactate accumulation, and that aerobic glycolysis accounts for 80% of ATP production in mature osteoblasts ( Figure 3 ) ( 40 , 41 ).…”