The microcirculation of mammals is an autoregulated and complex synchronised system according to the current demand for nutrients and oxygen. The undisturbed course of vital functions such as of growth, blood pressure...The microcirculation of mammals is an autoregulated and complex synchronised system according to the current demand for nutrients and oxygen. The undisturbed course of vital functions such as of growth, blood pressure regulation, inflammatory sequence and embryogenesis is bound to endothelial integrity. The sensible vasomotion is particularly dependent on it. Mechano-transduction signalling networks play a critical role in vital cellular processes and are the decisive physiological mechanism for an adequate NO-release, main responsible for the autoregulation of vessels. Disturbed endothelial integrity, originating, e.g., from chronic oxidative stress and/or mechanic (oscillatory) stress, leads to disturbance of vasomotion as well as a disequilibrium of redox systems, recognized as main cause for the development of chronic inflammation diseases such as atherosclerosis and corresponding secondary illnesses, possibly cancer. The endothelial cytoskeleton, which corresponds to a viscoelastic “tensegrity model”, offers the possibility for mechano-transduction via its special construction. The rapidly growing knowledge about mechanical forces in cellular sensing and regulation of the last years (that culminated in the Nobel Prize award for the decoding of pressure/vibration sensing ion channels), led us to the following hypothesis: The extern stressor “Noise” produces under certain conditions an oscillatory stress field in the physiologically laminar flow bed of capillaries, which is able to lead to irregular mechano-transductions. Findings provide a strict dependence on frequency in mechano-transduction with determination of thresholds for a 1:1 transmission. The knowledge, recently gained on endothelial mechano-transduction, sheds a new light on the importance of low frequencies. This could indicate the long-sought pathophysiological way in which infrasound can exert a stressor effect at the cellular level. Noise-exposed citizens, who live near infrastructures such as a biogas installation, heat pumps, block-type thermal power stations and bigger industrial wind turbines (IWT’s), show worldwide mainly a symptomatology associated with microcirculatory disorder. Conceivable are also effects on insects or fishes, since the piezo-channels are recognised as conserved structures of all multicellular organism. An experimental design is proposed to demonstrate the direct pathological influence of infrasound of defined strength, frequency, effect/time profile and duration on the sensitive vasomotion.展开更多
Orthodontic tooth movement(OTM)depends on periodontal ligament cells(PDLCs),which sense biomechanical stimuli and initiate alveolar bone remodeling.Light(optimal)forces accelerate OTM,whereas heavy forces decelerate i...Orthodontic tooth movement(OTM)depends on periodontal ligament cells(PDLCs),which sense biomechanical stimuli and initiate alveolar bone remodeling.Light(optimal)forces accelerate OTM,whereas heavy forces decelerate it.However,the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces(MFs)remain unclear.This study demonstrates that mechanosensitive ion channel Piezo1-medi-ated Ca^(2+)signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs un-der heavy-force conditions.Heavy MF up-regulated Piezo1 in PDLCs,reducing mitochondrial Ca^(2+)influx by inhibiting ITPR3 expression in mitochondria-associated membranes.Decreased mito-chondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS-STING signaling cascade,subsequently inhibiting monocyte-to-osteo-clast differentiation.Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM.These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling.This mechanism may be a potential therapeutic target for accelerating OTM.展开更多
文摘The microcirculation of mammals is an autoregulated and complex synchronised system according to the current demand for nutrients and oxygen. The undisturbed course of vital functions such as of growth, blood pressure regulation, inflammatory sequence and embryogenesis is bound to endothelial integrity. The sensible vasomotion is particularly dependent on it. Mechano-transduction signalling networks play a critical role in vital cellular processes and are the decisive physiological mechanism for an adequate NO-release, main responsible for the autoregulation of vessels. Disturbed endothelial integrity, originating, e.g., from chronic oxidative stress and/or mechanic (oscillatory) stress, leads to disturbance of vasomotion as well as a disequilibrium of redox systems, recognized as main cause for the development of chronic inflammation diseases such as atherosclerosis and corresponding secondary illnesses, possibly cancer. The endothelial cytoskeleton, which corresponds to a viscoelastic “tensegrity model”, offers the possibility for mechano-transduction via its special construction. The rapidly growing knowledge about mechanical forces in cellular sensing and regulation of the last years (that culminated in the Nobel Prize award for the decoding of pressure/vibration sensing ion channels), led us to the following hypothesis: The extern stressor “Noise” produces under certain conditions an oscillatory stress field in the physiologically laminar flow bed of capillaries, which is able to lead to irregular mechano-transductions. Findings provide a strict dependence on frequency in mechano-transduction with determination of thresholds for a 1:1 transmission. The knowledge, recently gained on endothelial mechano-transduction, sheds a new light on the importance of low frequencies. This could indicate the long-sought pathophysiological way in which infrasound can exert a stressor effect at the cellular level. Noise-exposed citizens, who live near infrastructures such as a biogas installation, heat pumps, block-type thermal power stations and bigger industrial wind turbines (IWT’s), show worldwide mainly a symptomatology associated with microcirculatory disorder. Conceivable are also effects on insects or fishes, since the piezo-channels are recognised as conserved structures of all multicellular organism. An experimental design is proposed to demonstrate the direct pathological influence of infrasound of defined strength, frequency, effect/time profile and duration on the sensitive vasomotion.
基金supported by the Natural Science Foundation of China (No.82471016,81470772)Chongqing Talent Program:Innovative Leading Talents (Medical Field,No.CQYC20210303384)+1 种基金Chongqing Medical Scientific Research Project (China) (No.cstc2020jcyj-msxmX0307)Youth Innovation in Future Medicine (Chongqing Medical University) (No.W0033).
文摘Orthodontic tooth movement(OTM)depends on periodontal ligament cells(PDLCs),which sense biomechanical stimuli and initiate alveolar bone remodeling.Light(optimal)forces accelerate OTM,whereas heavy forces decelerate it.However,the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities under different mechanical forces(MFs)remain unclear.This study demonstrates that mechanosensitive ion channel Piezo1-medi-ated Ca^(2+)signal conversion is crucial for sensing and delivering biomechanical signals in PDLCs un-der heavy-force conditions.Heavy MF up-regulated Piezo1 in PDLCs,reducing mitochondrial Ca^(2+)influx by inhibiting ITPR3 expression in mitochondria-associated membranes.Decreased mito-chondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS-STING signaling cascade,subsequently inhibiting monocyte-to-osteo-clast differentiation.Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM.These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling.This mechanism may be a potential therapeutic target for accelerating OTM.
