RANKL Mediates Muscle Atrophy and Dysfunction in a Cigarette Smoke–induced Model of Chronic Obstructive Pulmonary Disease

Xiong, Jing; Le, Yanqing; Rao, Yafei; Zhou, Lu; Hu, Yuhan; Guo, Sitong; Sun, Yongchang

doi:10.1165/rcmb.2020-0449oc

Cited by 30 publications

(22 citation statements)

References 42 publications

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“…CS extracts (CSE) was prepared as described in our previous study ( Xiong et al., 2021 ). In brief, five cigarettes were sucked through a 10-ml of RPMI-1640 medium at a constant velocity and then was sterilized via filtering through a 0.22-μm filter (Millipore, Burlington, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

Rao

Gai

et al. 2022

Front. Cell. Infect. Microbiol.

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AimSmoker COPD patients with chest radiological signs of prior tuberculosis (TB) showed more severe lung damage, but the mechanisms remain unclear. Emerging evidence has implicated NK cells in the pathogenesis of both COPD and TB. The purpose of this study was to delineate the profile and cytokine production of NK-cell subpopulations and their immunometabolic changes after exposure to both cigarette smoke (CS) and Mycobacterium tuberculosis(MTB).MethodsWe profiled NK-cell subpopulations in terms of percentage and cytokine production by flow cytometry in smoker patients with pulmonary TB (PTB). In an in vitro coexposure model, we investigated proinflammatory cytokine production, glycolytic influx, and oxidative phosphorylation of NK cells under CS extract (CSE) and PPD costimulation.ResultsPeripheral blood NK cells in smoker patients with active PTB (CS+PTB group) showed altered proportion of subpopulations and excessive proinflammatory cytokine expressions. In vitro, CSE- and PPD-coexposed NK-92 cells displayed enhanced proinflammatory cytokine production, concurrent with decreased glycolytic influx and oxidative phosphorylation.ConclusionSmoker patients with active PTB showed enhanced proinflammatory cytokine expression within altered NK cell subpopulations. CSE and PPD coexposure induced heightened cytokine production concurrent with impaired cell metabolism in NK cells. These novel data suggest a potential role of NK cells in the pathogenesis of lung injury in subjects with coexposure to CS and TB.

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Section: Methodsmentioning

confidence: 99%

Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

Rao

Gai

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Moreover, other conditions such as chronic cigarette usage or chronic obstructive pulmonary disease (COPD) correlate with high serum RANKL concentrations ( Bai et al, 2011 ; Nogueira and Breen, 2021 ) and low BMD and muscle dysfunction ( Nogueira and Breen, 2021 ). A 6-month chronic exposure to cigarette smoking increases RANK and RANKL concentrations in skeletal muscle fibers ( Xiong et al, 2021 ). Interestingly, the neutralization of RANKL restores muscle strength and function in mice exposed to tobacco smoke particles ( Xiong et al, 2021 ).…”

Section: The Rank/rankl/opg Pathway In Dystrophic Skeletal Muscle Inf...mentioning

confidence: 99%

“…A 6-month chronic exposure to cigarette smoking increases RANK and RANKL concentrations in skeletal muscle fibers ( Xiong et al, 2021 ). Interestingly, the neutralization of RANKL restores muscle strength and function in mice exposed to tobacco smoke particles ( Xiong et al, 2021 ). Furthermore, the exposure of muscle cells to tobacco smoke particles in vitro causes an increase in the expression of RANKL/RANK, which is responsible for the inflammation and atrophy of muscle fibers ( Xiong et al, 2021 ).…”

Section: The Rank/rankl/opg Pathway In Dystrophic Skeletal Muscle Inf...mentioning

confidence: 99%

“…Interestingly, the neutralization of RANKL restores muscle strength and function in mice exposed to tobacco smoke particles ( Xiong et al, 2021 ). Furthermore, the exposure of muscle cells to tobacco smoke particles in vitro causes an increase in the expression of RANKL/RANK, which is responsible for the inflammation and atrophy of muscle fibers ( Xiong et al, 2021 ). Lastly, mice with non-metastatic ovarian cancer exhibit cachexia associated with high RANKL concentrations, while an anti-RANKL treatment reduces bone loss and improves muscle function ( Pin et al, 2021 ).…”

Section: The Rank/rankl/opg Pathway In Dystrophic Skeletal Muscle Inf...mentioning

confidence: 99%

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The Roles of RANK/RANKL/OPG in Cardiac, Skeletal, and Smooth Muscles in Health and Disease

Marcadet

Bouredji

Argaw

et al. 2022

Front. Cell Dev. Biol.

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Although their physiology and functions are very different, bones, skeletal and smooth muscles, as well as the heart have the same embryonic origin. Skeletal muscles and bones interact with each other to enable breathing, kinesis, and the maintenance of posture. Often, muscle and bone tissues degenerate synchronously under various conditions such as cancers, space travel, aging, prolonged bed rest, and neuromuscular diseases. In addition, bone tissue, skeletal and smooth muscles, and the heart share common signaling pathways. The RANK/RANKL/OPG pathway, which is essential for bone homeostasis, is also implicated in various physiological processes such as sarcopenia, atherosclerosis, and cardiovascular diseases. Several studies have reported bone-skeletal muscle crosstalk through the RANK/RANKL/OPG pathway. This review will summarize the current evidence indicating that the RANK/RANKL/OPG pathway is involved in muscle function. First, we will briefly discuss the role this pathway plays in bone homeostasis. Then, we will present results from various sources indicating that it plays a physiopathological role in skeletal, smooth muscle, and cardiac functions. Understanding how the RANK/RANKL/OPG pathway interferes in several physiological disorders may lead to new therapeutic approaches aimed at protecting bones and other tissues with a single treatment.

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“…RANKL neutrolization attenuated skeletal muscle dysfunction and reduced the expression of myostatin and MuFR1/Atrogin1. In vitro , CS extract induced up-regulation of RANKL/RANK in skeletal muscle cells, and blocking RANKL down-regulated myostatin expression ( 93 ). These results indicate that the RANKL/RANK pathway plays a key role in skeletal muscle atrophy induced by chronic CS exposure.…”

Section: Muscle-bone Crosstalk In Copdmentioning

confidence: 99%

Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease

Zhang

Sun

2021

Front. Endocrinol.

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Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation and growth of skeletal muscles, but also regulate bone metabolism. Both irisin and myostatin have been shown to be dysregulated and associated with exercise and skeletal muscle dysfunction in COPD. During exercise, skeletal muscles produce a large amount of IL-6 which acts as a myokine, exerting at least two different conflicting functions depending on physiological or pathological conditions. Remarkably, IL-6 is highly expressed in COPD, and considered to be a biomarker of systemic inflammation, which is associated with both sarcopenia and bone loss. For osteokines, receptor activator of nuclear factor kappa-B ligand (RANKL), a classical regulator of bone metabolism, was recently found to play a critical role in skeletal muscle atrophy induced by chronic cigarette smoke (CS) exposure. In this focused review, we described evidence for myokines and osteokines in the pathogenesis of skeletal muscle dysfunction/sarcopenia and osteoporosis in COPD, and proposed muscle-bone crosstalk as an important mechanism underlying the coexistence of muscle and bone diseases in COPD.

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RANKL Mediates Muscle Atrophy and Dysfunction in a Cigarette Smoke–induced Model of Chronic Obstructive Pulmonary Disease

Cited by 30 publications

References 42 publications

Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke

The Roles of RANK/RANKL/OPG in Cardiac, Skeletal, and Smooth Muscles in Health and Disease

Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease

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