Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation

Jin, Zixue; Kho, Jordan; Dawson, Brian; Jiang, Mingming; Chen, Yuqing; Ali, Saima; Burrage, Lindsay C.; Grover, Monica; Palmer, D. Jason; Turner, Dustin L.; Ng, Philip; Nagamani, Sandesh C.S.; Lee, Brendan

doi:10.1172/jci138935

Cited by 49 publications

(36 citation statements)

References 72 publications

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“…Glycolysis is thought to preserve the “stemness” of the proliferating BMSCs [ 18 ]. However, some recent findings highlight that aerobic glycolysis is the predominant source of energy that promotes the differentiation of BMSCs [ [29] , [30] , [31] ]. The inhibition of glycolysis suppresses osteogenesis of primary bone marrow mesenchymal progenitors [ 29 ], while blunting glycolysis pathways in BMSC-like ST2 cells also leads to decreased osteogenesis and mineralization [ 30 ].…”

Section: Glucose Fatty Acids and Amino Acids Metabolism During Bmsc D...mentioning

confidence: 99%

“…However, some recent findings highlight that aerobic glycolysis is the predominant source of energy that promotes the differentiation of BMSCs [ [29] , [30] , [31] ]. The inhibition of glycolysis suppresses osteogenesis of primary bone marrow mesenchymal progenitors [ 29 ], while blunting glycolysis pathways in BMSC-like ST2 cells also leads to decreased osteogenesis and mineralization [ 30 ]. Moreover, glycolytic agonist promotes osteogenic differentiation of BMSCs via activation of RhoA/ROCK [ 31 ].…”

Section: Glucose Fatty Acids and Amino Acids Metabolism During Bmsc D...mentioning

confidence: 99%

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Update on the effects of energy metabolism in bone marrow mesenchymal stem cells differentiation

Ning¹,

Liu²,

Bi³

et al. 2022

Molecular Metabolism

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Section: Glucose Fatty Acids and Amino Acids Metabolism During Bmsc D...mentioning

confidence: 99%

Section: Glucose Fatty Acids and Amino Acids Metabolism During Bmsc D...mentioning

confidence: 99%

Update on the effects of energy metabolism in bone marrow mesenchymal stem cells differentiation

Ning¹,

Liu²,

Bi³

et al. 2022

Molecular Metabolism

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“…NO is essential to control and balance periodontal stem cell differentiation, promoting osteogenic differentiation rather than adipogenic ( Yang et al, 2018 ), and has anabolic effects in bone, promoting osteoblast differentiation and glucose metabolism. NO production depends on arginine synthesis via the enzyme argininosuccinate lyase and its production is negatively modulated by control mechanisms such as nitric oxide synthase binding by caveolin-1 ( Jin et al, 2021 ). NO release may be triggered by RANKL; since inhibition of RANKL-induced NO increases osteoclastogenesis and bone resorption, osteoclastogenesis in response to RANKL is probably diminished by NO production ( Huang et al, 2017 ) ( Figure 3 ).…”

Section: Oxidative Stress In Bone Homeostasismentioning

confidence: 99%

In Sickness and in Health: The Oxygen Reactive Species and the Bone

Reis

Ramos

2021

Front. Bioeng. Biotechnol.

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Oxidative stress plays a central role in physiological and pathological bone conditions. Its role in signalment and control of bone cell population differentiation, activity, and fate is increasingly recognized. The possibilities of its use and manipulation with therapeutic goals are virtually unending. However, how redox balance interplays with the response to mechanical stimuli is yet to be fully understood. The present work summarizes current knowledge on these aspects, in an integrative and broad introductory perspective.

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“…The inhibition of nitric oxide production by interrupting argininosuccinate lyase represses aerobic glycolysis and osteoblastic activity. Mice deficient in argininosuccinate lyase develops low bone mass and less osteogenic differentiation capacity than wild type mice [ 18 ]. Loss of the leucine-rich repeat-containing G protein coupled receptor 4 (Lgr4) increases aerobic glycolysis and induces osteogenesis loss of osteoprogenitor cells.…”

Section: The Role Of Mitochondrial Homeostasis In Bone-forming Cell Functionmentioning

confidence: 99%

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

Wang

Chen

et al. 2021

Antioxidants

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Bone-forming cells build mineralized microstructure and couple with bone-resorbing cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moderate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting bone anabolism to compromise osteoporosis development. A plethora of molecules, including ion channels, integrins, focal adhesion kinases, and myokines, are mechanosensitive and transduce mechanical stimuli into intercellular signaling, regulating growth, mineralized extracellular matrix biosynthesis, and resorption. Mechanical stimulation changes mitochondrial respiration, biogenesis, dynamics, calcium influx, and redox, whereas mechanical disuse induces mitochondrial dysfunction and oxidative stress, which aggravates bone-forming cell apoptosis, senescence, and dysfunction. The control of the mitochondrial biogenesis activator PGC-1α by NAD+-dependent deacetylase sirtuins or myokine FNDC/irisin or repression of oxidative stress by mitochondrial antioxidant Nrf2 modulates the biophysical stimulation for the promotion of bone integrity. This review sheds light onto the roles of mechanosensitive signaling, mitochondrial dynamics, and antioxidants in mediating the anabolic effects of biophysical stimulation to bone tissue and highlights the remedial potential of mitochondrial biogenesis regulators for osteoporosis.

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Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation

Cited by 49 publications

References 72 publications

Update on the effects of energy metabolism in bone marrow mesenchymal stem cells differentiation

Update on the effects of energy metabolism in bone marrow mesenchymal stem cells differentiation

In Sickness and in Health: The Oxygen Reactive Species and the Bone

Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics

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