Energy metabolism in osteoclast formation and activity

Lemma, Silvia; Sboarina, Martina; Porporato, Paolo E.; Zini, Nicoletta; Sonveaux, Pierre; Pompo, Gemma Di; Baldini, Nicola; Avnet, Sofia

doi:10.1016/j.biocel.2016.08.034

Cited by 161 publications

(174 citation statements)

References 52 publications

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“…3). The increase in OXPHOS is consistent with a substantial increase in the number, the size and the cristae abundance of mitochondria with osteoclast differentiation [46]. Interestingly, osteoclastogenesis appeared to be optimal with glucose at approximately 5 mM in the in vitro differentiation system, whereas high levels of glucose such as 20 mM were less effective even though cell proliferation was maximally stimulated.…”

Section: Glucose Metabolism In Osteoclastsmentioning

confidence: 68%

“…Similarly, limiting glucose metabolism by either omission of glucose in the culture media or knockdown of Hif1a reduced bone resorption by murine osteoclasts in vitro [48]. More recently, human osteoclasts were shown to rely on glycolysis for bone resorption, as reducing the rate of glycolysis with galactose significantly impaired collagen I degradation whereas suppression of the mitochondrial complex I with a non-cytotoxic dose of rotenone enhanced osteoclast activity [46]. Interestingly, immunostaining experiments revealed that some of the key glycolytic enzymes were localized to the actin ring of polarized osteoclasts attached to bone surface [46].…”

Section: Glucose Metabolism In Osteoclastsmentioning

confidence: 99%

“…More recently, human osteoclasts were shown to rely on glycolysis for bone resorption, as reducing the rate of glycolysis with galactose significantly impaired collagen I degradation whereas suppression of the mitochondrial complex I with a non-cytotoxic dose of rotenone enhanced osteoclast activity [46]. Interestingly, immunostaining experiments revealed that some of the key glycolytic enzymes were localized to the actin ring of polarized osteoclasts attached to bone surface [46]. Therefore, in contrast to osteoclastogenesis that requires mitochondrial OXPHOS fueled by both glucose and potentially other substrates, the mature osteoclasts appear to rely heavily on active aerobic glycolysis to support bone resorption.…”

Section: Glucose Metabolism In Osteoclastsmentioning

confidence: 99%

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Glucose metabolism in bone

Karner

Long

2018

Bone

115

110

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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.

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Section: Glucose Metabolism In Osteoclastsmentioning

confidence: 68%

Section: Glucose Metabolism In Osteoclastsmentioning

confidence: 99%

Section: Glucose Metabolism In Osteoclastsmentioning

confidence: 99%

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Glucose metabolism in bone

Karner

Long

2018

Bone

115

110

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“…Conversely, the proteins involved in the metabolic pathways of glycolysis, the TCA cycle, and oxidative phosphorylation were all upregulated during RANKL-stimulated osteoclastogenesis; the ATP consumption in bone resorption associated with bone matrix degradation was mainly derived from glycolysis [22]. In vitro quantitative proteomics results also indicated that DEPs involved in energy metabolism play an important role in osteoclastogenesis and bone resorption [25, 26].…”

Section: Discussionmentioning

confidence: 99%

Energy Metabolism in the Bone is Associated with Histomorphometric Changes in Rats with Hyperthyroidism

Lai

et al. 2018

Cell Physiol Biochem

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Background/Aims: In this study we assessed histomorphometric changes induced by thyroxine (T4) in 3-month-old hyperthyroid male rats and examined whether the potential mechanism of these changes is related to bone changes. Methods: Rats were classified as either hyperthyroid following administration of 250 µg/kg/day freshly prepared T4 by gavage for 2 months or euthyroid following administration of vehicle alone (n = 8 per group). We measured bone mineral density (BMD), bone biomechanical properties, and bone histomorphometric changes. Levels of serum indicators were also measured, and three right femurs from the two groups were selected for proteomic investigation. Results: Compared with the control rats, hyperthyroid rats showed a reduction in the fifth lumbar vertebral BMD as well as in the entire femoral BMD (p = 0.033 and 0.026, respectively). Histomorphometric analysis of the proximal tibial metaphysis showed that the percentage of the trabecular area, trabecular number, and percentage of the cortical bone area in the hyperthyroid rats significantly decreased compared with those of the control rats. Conversely, bone formation rate (per unit of bone surface and bone volume), percentage of the osteoclast perimeter, trabecular separation, and endosteal mineral apposition rate in the hyperthyroid rats significantly increased compared with the control rats (all p < 0.05). Except for stiffness (p = 0.24), all bone biomechanical properties of the femur showed a significant decreasing trend in the hyperthyroid rats versus the control rats (all p < 0.05). Serum levels of osteocalcin, alkaline phosphatase, terminal telopeptides of type β collagen, and tartrate-resistant acid phosphatase were higher in the hyperthyroid rats than in the control rats (all p < 0.05). Using isobaric tags for relative and absolute quantification (iTRAQ), the expression levels of 1,310 proteins were found to be significantly different between the hyperthyroid and control rats (711 proteins were upregulated and 599 were downregulated in hyperthyroid rats). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that most of the enzymes in the glycolysis–tricarboxylic acid (TCA) cycle–oxidative phosphorylation signalling pathway were upregulated in hyperthyroid rats, and seven differentially expressed proteins were selected to verify the iTRAQ results using western blotting. Conclusion: Energy metabolism via the glycolysis–TCA cycle–oxidative phosphorylation pathway is positively associated with T4-induced bone histomorphometric changes in rats.

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“…For example, differentiating osteoblasts rely heavily upon glucose utilization (Esen et al 2013; Esen et al 2015) and produce lactate as a result (Felix et al 1978). During osteoclastogenesis, mitochondrial mass within the cell is high and the formation of osteoclasts correlates to elevated rates of oxidative phosphorylation, as reviewed by Lemma et al 2016. Yet during bone resorption, glycolysis is the predominant pathway (Lemma et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone

Prisby

2017

Journal of Endocrinology

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Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair, and provides O2, nutrients, waste elimination, systemic hormones, and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow. It is becoming increasingly clear that the vascular and skeletal systems are intimately linked in metabolic regulation and physiological and pathological processes. This review examines how agents such as mechanical loading, parathyroid hormone, estrogen, vitamin D and calcitonin, all considered anabolic for bone, have tremendous impacts on the bone vasculature. In fact, these agents influence bone blood vessels prior to impacting bone. Further, data reveal strong associations between vasodilator capacity of bone blood vessels and trabecular bone volume, and poor associations between estrogen status and uterine mass and trabecular bone volume. Additionally, this review highlights the importance of the bone microcirculation, particularly the vascular endothelium and NO-mediated signaling, in the regulation of bone blood flow, bone interstitial fluid flow and pressure, and the paracrine signaling of bone cells. Finally, the vascular endothelium as a mediator of bone health and disease is considered.

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Energy metabolism in osteoclast formation and activity

Cited by 161 publications

References 52 publications

Glucose metabolism in bone

Glucose metabolism in bone

Energy Metabolism in the Bone is Associated with Histomorphometric Changes in Rats with Hyperthyroidism

Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone

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