scholarly journals Aging Induced p53/p21 in Genioglossus Muscle Stem Cells and Enhanced Upper Airway Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Lu-Ying Zhu ◽  
Li-Ming Yu ◽  
Wei-Hua Zhang ◽  
Jia-Jia Deng ◽  
Shang-Feng Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Muscle Injury ◽  
Myogenic Differentiation ◽  
Upper Airway ◽  
Damage Mechanism ◽  
Muscle Stem Cells ◽  
Airway Injury ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Aging Muscle

Aging of population brings related social problems, such as muscle attenuation and regeneration barriers with increased aging. Muscle repair and regeneration depend on muscle stem cells (MuSCs). Obstructive sleep apnea (OSA) rises in the aging population. OSA leads to hypoxia and upper airway muscle injury. However, little is known about the effect of increasing age and hypoxia to the upper airway muscle. The genioglossus (GG) is the major dilator muscle to keep the upper airway open. Here, we reported that muscle fiber and MuSC function declined with aging in GG. Increasing age also decreased the migration and proliferation of GG MuSCs. p53 and p21 were high expressions both in muscle tissue and in GG MuSCs. We further found that hypoxia inhibited GG MuSC proliferation and decreased myogenic differentiation. Then, hypoxia enhanced the inhibition effect of aging to proliferation and differentiation. Finally, we investigated that hypoxia and aging interact to form a vicious circle with upregulation of p53 and p21. This vicious hypoxia plus aging damage accelerated upper airway muscle injury. Aging and hypoxia are the major damage elements in OSA patients, and we propose that the damage mechanism of hypoxia and aging in GG MuSCs will help to improve upper airway muscle regeneration.

scholarly journals Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation

2016 ◽  
Vol 48 (5) ◽  
pp. 1340-1350 ◽  
Author(s):  
Luigi Taranto-Montemurro ◽  
Scott A. Sands ◽  
Bradley A. Edwards ◽  
Ali Azarbarzin ◽  
Melania Marques ◽  
...  
Keyword(s):  
Crossover Trial ◽  
Positive Airway Pressure ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Double Blind ◽  
Healthy Humans ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility

We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea–hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V′0,passive) and active (V′0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced activePcrit(median (interquartile range) −5.2 (4.3) cmH2O on desipramineversus−1.9 (2.7) cmH2O on placebo; p=0.049) but not passivePcrit(−2.2 (3.4)versus−0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined asV′0,active−V′0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.

scholarly journals Upper airway muscle activity in normal women: influence of hormonal status

1998 ◽  
Vol 84 (3) ◽  
pp. 1055-1062 ◽  
Author(s):  
Rainer M. Popovic ◽  
David P. White
Keyword(s):  
Postmenopausal Women ◽  
Muscle Activity ◽  
Airway Resistance ◽  
Upper Airway ◽  
Resistive Load ◽  
Substantial Impact ◽  
Upper Airway Resistance ◽  
Female Hormones ◽  
Dilator Muscle ◽  
Obstructive Sleep

Obstructive sleep apnea is a disorder with a strong male predominance. One possible explanation could be an effect of female hormones on pharyngeal dilator muscle activity. Therefore, we determined the level of awake genioglossus electromyogram (EMGgg) and upper airway resistance in 12 pre- and 12 postmenopausal women under basal conditions and during the application of an inspiratory resistive load (25 cmH2O ⋅ l−1 ⋅ s). In addition, a subgroup of eight postmenopausal women were studied a second time after 2 wk of combined estrogen and progesterone replacement in standard doses. Peak phasic and tonic genioglossus activity, expressed as a percentage of maximum, were highest in the luteal phase of the menstrual cycle (phasic 23.9 ± 3.8%, tonic 10.2 ± 1.0%), followed by the follicular phase (phasic 15.5 ± 2.2%, tonic 7.3 ± 0.8%), and were lowest in the postmenopausal group (phasic 11.3 ± 1.6%, tonic of 5.0 ± 0.6), whereas upper airway resistance did not differ. There was a weak but significant positive correlation between progesterone levels and both peak phasic ( P < 0.05) and tonic ( P < 0.01) EMGgg. Finally, there was a significant increase in EMGgg in the postmenopausal group restudied after hormone therapy. In conclusion, female hormones (possibly progesterone) have a substantial impact on upper airway dilator muscle activity.

scholarly journals The Expression Profiles of mRNAs and lncRNAs in Buffalo Muscle Stem Cells Driving Myogenic Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruimen Zhang ◽  
Jinling Wang ◽  
Zhengzhong Xiao ◽  
Chaoxia Zou ◽  
Qiang An ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Myogenic Differentiation ◽  
Expression Profiles ◽  
Meat Production ◽  
Rna Regulation ◽  
Muscle Stem Cells ◽  
Lncrna Expression ◽  
P53 Signaling

Buffalo breeding has become an important branch of the beef cattle industry. Hence, it is of great significance to study buffalo meat production and meat quality. However, the expression profiles of mRNA and long non-coding RNAs (lncRNA) molecules in muscle stem cells (MuSCs) development in buffalo have not been explored fully. We, therefore, performed mRNA and lncRNA expression profiling analysis during the proliferation and differentiation phases of MuSCs in buffalo. The results showed that there were 4,820 differentially expressed genes as well as 12,227 mRNAs and 1,352 lncRNAs. These genes were shown to be enriched in essential biological processes such as cell cycle, p53 signaling pathway, RNA transport and calcium signaling pathway. We also identified a number of functionally important genes, such as MCMC4, SERDINE1, ISLR, LOC102394806, and LOC102403551, and found that interference with MYLPF expression significantly inhibited the differentiation of MuSCs. In conclusion, our research revealed the characteristics of mRNA and lncRNA expression during the differentiation of buffalo MuSCs. This study can be used as an important reference for the study of RNA regulation during muscle development in buffalo.

scholarly journals A long noncoding RNA,LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression

2020 ◽  
Vol 117 (51) ◽  
pp. 32464-32475
Author(s):  
Anqi Dong ◽  
Christopher B. Preusch ◽  
Wai-Kin So ◽  
Kangning Lin ◽  
Shaoyuan Luan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Target Genes ◽  
Myogenic Differentiation ◽  
Critical Role ◽  
Chromatin Accessibility ◽  
Mechanistic Study ◽  
Muscle Stem Cells ◽  
Myogenic Lineage

Epigenetics regulation plays a critical role in determining cell identity by controlling the accessibility of lineage-specific regulatory regions. In muscle stem cells, epigenetic mechanisms of how chromatin accessibility is modulated during cell fate determination are not fully understood. Here, we identified a long noncoding RNA,LncMyoD, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion ofLncMyoDin muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation.LncMyoDexclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss ofLncMyoDprevents the establishment of a permissive chromatin environment at myogenic E-box–containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion ofLncMyoDstrongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows thatLncMyoDassociates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.

Reduced genioglossal activity with upper airway anesthesia in awake patients with OSA

2000 ◽  
Vol 88 (4) ◽  
pp. 1346-1354 ◽  
Author(s):  
Robert B. Fogel ◽  
Atul Malhotra ◽  
Steven A. Shea ◽  
Jill K. Edwards ◽  
David P. White
Keyword(s):  
Muscle Activity ◽  
Upper Airway ◽  
Significant Rise ◽  
Tidal Breathing ◽  
Airflow Resistance ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Airway Mechanics ◽  
Airway Collapsibility ◽  
Negative Airway Pressure

We examined whether topical upper airway anesthesia leads to a reduction in genioglossal (GG) electromyogram (EMG) in patients with obstructive sleep apnea (OSA). Airway mechanics were also evaluated. In 13 patients with OSA, we monitored GG EMG during tidal breathing and during the application of pulses of negative airway pressure (−10 to −12 cmH2O). Airflow resistance and airway collapsibility were determined. All measurements were performed with and without topical anesthesia (lidocaine). Anesthesia led to a significant fall in the peak GG EMG response to negative pressure from 36.1 ± 4.7 to 24.8 ± 5.3% (SE) of maximum ( P < 0.01). This was associated with a fall in phasic and tonic EMG during tidal breathing (phasic from 24.4 ± 4.1 to 16.4 ± 3.4% of maximum and tonic from 10.9 ± 1.6 to 8.0 ± 1.3% of maximum, P < 0.01). A significant rise in pharyngeal airflow resistance was also observed. Our results demonstrate that topical receptor mechanisms in the nasopharynx importantly influence dilator muscle activity and are likely important in driving the augmented dilator muscle activity seen in the apnea patient.

Long-term facilitation of ventilation is not present during wakefulness in healthy men or women

2002 ◽  
Vol 93 (6) ◽  
pp. 2129-2136 ◽  
Author(s):  
A. S. Jordan ◽  
P. G. Catcheside ◽  
F. J. O'Donoghue ◽  
R. D. McEvoy
Keyword(s):  
Repeated Measures ◽  
Human Subjects ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Menstrual Phase ◽  
Healthy Human ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are unclear. The stability of the respiratory controller has been proposed to be important in OSA pathogenesis and may be involved in the gender difference in prevalence. Repetitive hypoxia elicits a progressive rise in ventilation in animals [long-term facilitation (LTF)]. There is uncertainty whether LTF occurs in humans, but if present it may stabilize respiration and possibly also the upper airway. This study was conducted to determine 1) whether LTF exists during wakefulness in healthy human subjects and, if so, whether it is more pronounced in women than men and 2) whether inspiratory pump and upper airway dilator muscle activities are affected differently by repetitive hypoxia. Twelve healthy young men and ten women in the luteal menstrual phase were fitted with a nasal mask and intramuscular genioglossal EMG (EMGgg) recording electrodes. After 5 min of rest, subjects were exposed to ten 2-min isocapnic hypoxic periods (∼9% O2 in N2, arterial O2 saturation ∼80%) separated by 2 min of room air. Inspired minute ventilation (V˙i) and peak inspiratory EMGgg activity were averaged over 30-s intervals, and respiratory data were compared between genders during and after repetitive hypoxia by using ANOVA for repeated measures. V˙i during recovery from repetitive hypoxia was not different from the resting level and not different between genders. There was no facilitation of EMGgg activity during or after repetitive hypoxia. EMGgg activity was reduced below baseline during recovery from repetitive hypoxia in women. In conclusion, we have found no evidence of LTF of ventilation or upper airway dilator muscle activity in healthy subjects during wakefulness.

Alae nasi electromyographic activity and timing in obstructive sleep apnea

1985 ◽  
Vol 58 (4) ◽  
pp. 1252-1256 ◽  
Author(s):  
P. M. Suratt ◽  
R. McTier ◽  
S. C. Wilhoit
Keyword(s):  
Eye Movement ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Esophageal Pressure ◽  
Emg Activity ◽  
Electromyographic Activity ◽  
Rapid Eye Movement ◽  
Rib Cage ◽  
Dilator Muscle ◽  
Obstructive Sleep

The alae nasi is an accessible dilator muscle of the upper airway located in the nose. We measured electromyograms (EMG) of the alae nasi to determine the relationship between their activity and timing to contraction of the rib cage muscles and diaphragm during obstructive apnea in nine patients. Alae nasi EMG were measured with surface electrodes and processed to obtain a moving time average. Contraction of the rib cage and diaphragm during apneas was detected with esophageal pressure. During non-rapid-eye-movement (NREM) sleep, there was a significant correlation in each patient between alae nasi EMG activity and the change in esophageal pressure. During rapid-eye-movement (REM) sleep, correlations were significantly lower than during NREM sleep. As the duration of each apnea increased, the activation of alae nasi EMG occurred progressively earlier than the change in esophageal pressure. We conclude that during obstructive apneas in NREM sleep, activity of the alae nasi increases when diaphragm and rib cage muscle force increases and the activation occurs earlier as each apneic episode progresses.

scholarly journals Noggin Combined With Dental Pulp Stem Cells Repair Muscle Injury Through Smad/Pax7 Signaling Pathway

2021 ◽  
Author(s):  
Meng-Han Zhang ◽  
Li-Ming Yu ◽  
Wei-Hua Zhang ◽  
Jia-Jia Deng ◽  
Bing-Jing Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Satellite Cell ◽  
Morphometric Analysis ◽  
Muscle Regeneration ◽  
Dental Pulp ◽  
Tibialis Anterior ◽  
Muscle Injury ◽  
Myogenic Differentiation ◽  
Tibialis Anterior Muscle

Abstract Background: A proper stem cell source is key to muscle injury repair. Dental pulp stem cells (DPSCs) are an available source for the treatment of muscle injury due to their high reproductive and differential activities. However, the application of DPSCs in muscle regeneration is incompletely understood. Noggin, a secreted BMP antagonist promoted by Wnt-1, is required for embryonic myogenesis. Our research is to study whether Noggin can promote myogenic differentiation of DPSCs, and then to investigate the repair effect of Noggin combined with DPSCs in muscle injury.Methods: DPSCs were treated with Noggin to induce myogenic differentiation in vitro. The levels of myogenic markers (MyoD, Desmin, MRF4 and MyHC), and satellite cell markers (Pax3, Pax7, Six1 and Eya2) were detected during this process. Next, we blocked the effect of Noggin by adding BMP, and Samd phosphorylation level was tested. Then, we implanted Noggin-pretreated DPSC combined Matrigel into the mouse tibialis anterior muscle with volumetric muscle loss (VML). After 30-day recovery, morphometric analysis of the tibialis anterior muscle was performed.Results: Noggin effectively increased myotube formation in DPSCs. We also found Noggin accelerated the skeletal myogenic differentiation of DPSCs and promote Pax7+ satellite-like cell generation. These satellite-like cells had the capacity to generate myofibers and could self-renew. Pax7 and Pax3 levels were repressed when blocked the effect of Noggin by adding BMP, and Noggin eliminated the level of BMP/Smad phosphorylation. This suggested that Noggin facilitated the skeletal myogenic differentiation of DPSCs via Smad/Pax7 pathway. Morphometric analysis of muscle cross-sections revealed that DPSCs therapy could increase repair size and decrease scar tissue in tibialis anterior muscle of VML. Moreover, Noggin-treated DPSCs can benefit to Pax7+ satellite cell pool and promote muscle regeneration. Conclusions: This work reveals that Noggin can promote the generation of satellite-like cells for the myogenic process in DPSCs through Smad/Pax7 signaling pathway, and these satellite-like cells bioconstructs might possess a relatively fast capacity to regenerate for muscle injury.

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