Glucose metabolism in bone

Abstract

The adult human skeleton is a multifunctional organ undergoing constant remodeling through the opposing activities of the bone-resorbing osteoclast and the bone-forming osteoblast. The exquisite balance between bone resorption and bone formation is responsible for bone homeostasis in healthy adults. However, evidence has emerged that such a balance is likely disrupted in diabetes where systemic glucose metabolism is dysregulated, resulting in increased bone frailty and osteoporotic fractures. These findings therefore underscore the significance of understanding the role and regulation of glucose metabolism in bone under both normal and pathological conditions. Recent studies have shed new light on the metabolic plasticity and the critical functions of glucose metabolism during osteoclast and osteoblast differentiation. Moreover, these studies have begun to identify intersections between glucose metabolism and the growth factors and transcription factors previously known to regulate osteoblasts and osteoclasts. Here we summarize the current knowledge in the nascent field, and suggest that a fundamental understanding of glucose metabolic pathways in the critical bone cell types may open new avenues for developing novel bone therapeutics.

Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health

“…Recent studies have elucidated the role of glucose metabolism in maintaining bone homeostasis. It has been shown that glucose metabolism is required for osteoblast and osteoclast differentiation, as well as for cell‐type–specific processes including matrix deposition and resorption . In order to assess the impact of MCT4 deletion on vertebral bone health, we compared the cortical and trabecular bone morphology in the caudal and lumbar vertebrae from 14‐month‐old WT and MCT4 KO mice using μCT.…”

“…One interpretation of these results is that glucose metabolism is affected in the resident trabecular bone cells: the osteoblasts and osteoclasts. Although the effect of lactate accumulation in these cells has not been studied in detail, it is known that they rely on glucose uptake for cell differentiation and bone formation . In fact, recent studies showed that osteoblasts preferentially use glycolysis for ATP production, even under aerobic conditions, mimicking the Warburg effect .…”

Bone: Another potential target to treat, prevent and predict diabetes

“…Glucose metabolism in the skeleton under physiological and pathological conditions has been deeply scrutinized . Unlike classical glucose‐handling organs such as muscle, liver and white adipose tissue, aerobic glycolysis is the major pathway for the utilization of glucose by the skeleton .…”

“…Osteoclasts are well established as being rich in mitochondria; osteoclastic bone resorption normally proceeds much more rapidly than osteoblastic bone formation, and its requirement for energy is, presumably, high . However, no data are available regarding how much glucose osteoclasts take up to perform their activities.…”

“…Glucose metabolism in the skeleton under physiological and pathological conditions has been deeply scrutinized. 21 Unlike classical glucosehandling organs such as muscle, liver and white adipose tissue, aerobic glycolysis is the major pathway for the utilization of glucose by the skeleton. 22,23 Many key enzymes associated with the glycolytic pathway in carbohydrate metabolism in the liver and muscle, including hexokinase II, lactate dehydrogenase A and pyruvate dehydrogenase kinase, are also present in osteoblasts 24,25 and osteoclasts.…”