Piezo1‐mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor‐β1

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(9)

Published: March 7, 2023

Macrophages are multifunctional immune system cells that essential for the mechanical stimulation-induced control of metabolism. Piezo1 is a non-selective calcium channel expressed in multifarious tissues to convey signals. Here, cellular model tension was used study effect stretch on phenotypic transformation macrophages and its mechanism. An indirect co-culture explore macrophage activation bone marrow mesenchymal stem (BMSCs), treadmill running validate mechanism vivo vitro studies. p53 acetylated deacetylated by as result strain being detected Piezo1. This process able polarize towards M2 secretes transforming growth factor-beta (TGF-β1), which subsequently stimulates BMSCs migration, proliferation osteogenic differentiation. Knockdown inhibits conversion reparative phenotype, thereby affecting remodelling. Blockade TGF-β I, II receptors significantly reduced exercise-increased mass mice. In conclusion, we showed causes influx, deacetylation, polarization TGF-β1 release through These events support BMSC osteogenesis.

Language: Английский

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Bone Repairment via Mechanosensation of Piezo1 Using Wearable Pulsed Triboelectric Nanogenerator

Small, Journal Year: 2022, Volume and Issue: 18(30)

Published: June 1, 2022

Abstract Bone repair in real time is a challenging medical issue for elderly patients; this mainly because aged bone marrow mesenchymal stem cells (BMSCs) possess limited osteogenesis potential and capacity. In study, triboelectric stimulation technology used to achieve via mechanosensation of Piezo1 by fabricating wearable pulsed nanogenerator (WP‐TENG) driven human body movement. A peak value 30 µA has the optimal effects rejuvenate BMSCs, enhance their osteogenic differentiation, promote umbilical vein endothelial cell tube formation. Further, previous studies demonstrate that WP‐TENG can reinforce BMSCs angiogenesis (HUVECs). Mechanistically, are rejuvenated mechanosensitive ion channel Piezo1. Thus, enhanced formation capacity HUVECs improved, which further confirmed augmented regeneration vivo investigations. This study provides signal transduction mechanism rejuvenating theoretical basis using generated WP‐TENG.

Language: Английский

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The role of PIEZO ion channels in the musculoskeletal system

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 324(3), P. C728 - C740

Published: Jan. 31, 2023

PIEZO1 and PIEZO2 are mechanosensitive cation channels that highly expressed in numerous tissues throughout the body exhibit diverse, cell-specific functions multiple organ systems. Within musculoskeletal system, to maintain muscle bone mass, sense tendon stretch, regulate senescence apoptosis response mechanical stimuli within cartilage intervertebral disc. is essential for transducing pain touch sensations as well proprioception nervous which can affect health. have been shown act both independently synergistically different cell types. Conditions alter PIEZO channel mechanosensitivity, such inflammation or genetic mutations, drastic effects on these functions. For this reason, therapeutic approaches PIEZO-related disease focus altering and/or activity a controlled manner, either through inhibition with small molecules, dietary control supplementation healthy membrane composition. Although many opportunities better understand remain, studies summarized review highlight how crucial health point promising possible avenues their modulation target.

Language: Английский

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Piezo1 regulates colon stem cells to maintain epithelial homeostasis through SCD1-Wnt-β-catenin and programming fatty acid metabolism

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115400 - 115400

Published: March 1, 2025

Highlights•Piezo1 inhibition promotes colon stem cell proliferation•SCD1 is downstream of Piezo1 to affect stemness•Impaired stemness associated with fatty acid metabolism in crypts•GsMTX4 has a protective effect on injured colitis colonoidsSummaryPiezo1, which maintains the integrity and function intestinal epithelial barrier, essential for colonic homeostasis. However, whether how regulates fate remains unclear. Here, we show that proliferation. Mechanistically, stearoyl-CoA 9-desaturase 1 (SCD1) by acting Wnt-β-catenin pathway. For mice, altered after knockdown activation was accompanied reprogrammed (FA) crypts. Notably, found GsMTX4 protects mouse human organoids. Our results elucidated role regulating normal postinjury fates through SCD1-Wnt-β-catenin SCD1-mediated FA desaturation process. These provide fresh perspectives mechanical factors therapeutic strategies related diseases.Graphical abstract

Language: Английский

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Mechanosensitive ion channels in apoptosis and ferroptosis: focusing on the role of Piezo1

BMB Reports, Journal Year: 2023, Volume and Issue: 56(3), P. 145 - 152

Published: Jan. 31, 2023

Mechanosensitive ion channels sense mechanical stimuli applied directly to the cellular membranes or indirectly through their tethered components, provoking mechanoresponses.Among others, Piezo1 mechanosensitive channel is a relatively novel Ca 2+ -permeable that primarily present in non-sensory tissues.Recent studies have demonstrated plays an important role -dependent cell death, including apoptosis and ferroptosis, presence of stimuli.It has also been proven cancer cells are sensitive stresses due higher expression levels compared normal cells.In this review, we discuss Piezo1-mediated death mechanisms therapeutic strategies inhibit induce by modulating activity with pharmacological drugs perturbations induced stretch ultrasound.

Language: Английский

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Mechanosensitive Piezo1 channel in physiology and pathophysiology of the central nervous system

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102026 - 102026

Published: July 31, 2023

Since the discovery of mechanosensitive Piezo1 channel in 2010, there has been a significant amount research conducted to explore its regulatory role physiology and pathology various organ systems. Recently, growing body compelling evidence emerged linking activity health disease central nervous system. However, exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes current on implications for system mechanobiology, retrospects results demonstrating cell types within system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, brain endothelial cells. Furthermore, discusses understanding involvement disorders, such as Alzheimer's disease, multiple sclerosis, glaucoma, stroke, glioma.

Language: Английский

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Mechanical force drives the initial mesenchymal-epithelial interaction during skin organoid development

Theranostics, Journal Year: 2023, Volume and Issue: 13(9), P. 2930 - 2945

Published: Jan. 1, 2023

Rationale: Stem cells self-organize to form organoids that generate mini-organs resemble the physiologically-developed ones.The mechanism by which stem acquire initial potential for generating remains elusive.Here we used skin as an example study how mechanical force drives epidermal-dermal interaction potentiates regenerate hair follicles.Methods: Live imaging analysis, single-cell RNA-sequencing and immunofluorescence were analyze contractile of dermal in organoids.Bulk calcium probe detection, functional perturbations verify signaling pathways respond cells.In vitro loading experiment was prove stretching triggers epidermal Piezo1 expression negatively regulates cell attachment.Transplantation assay test regenerative ability organoids.Results: We found cell-derived contraction movement surrounding aggregates trigger mesenchymal-epithelial (MEI).In response force, arrangement cytoskeleton regulated pathway further influences dermal-epidermal attachment.The native generated from exerts a on adjacent cells, activating sensor basal during organoid culture.Epidermal turn strong MEI regulate attachment.Proper mechanical-chemical coupling culture is required regeneration upon transplantation into back nude mice. Conclusion:Our demonstrated cascade event development, fundamental organoid, developmental, biology fields.

Language: Английский

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Multifunctional CeO2 nanozymes for mitigating high-glucose induced senescence and enhancing bone regeneration in type 2 diabetes mellitus

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 485, P. 149842 - 149842

Published: Feb. 19, 2024

Healing bone defects in patients with type 2 diabetes mellitus (T2DM) has long been a challenging issue. Elevated blood sugar levels T2DM lead to the overproduction of reactive oxygen species (ROS), which negatively affects mitochondrial function, induces senescence marrow mesenchymal stem cells (BMSCs), and diminishes their osteoblastic potential. In this study, we developed polyacrylic acid modified cerium oxide nanoparticles (PCNPs), biocompatible, water-soluble, antioxidant nanozyme. Our vitro experiments demonstrated that PCNPs effectively eliminated ROS, restored significantly upregulated AMPK-SIRT1-PGC1α signaling pathway, ultimately mitigating BMSCs senescence. Considering clinical applications, have also investigated synergistic effects material systems for sustained release vivo. This sustained-release system proved be more effective promoting defect healing rats. These findings introduce promising innovative approach managing using customized multifunctional nanozymes.

Language: Английский

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The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6616 - 6616

Published: June 14, 2022

Piezo1 channels are highly mechanically-activated cation that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize emerging evidence of channel-mediated effects physiology muscle, with a particular focus on role controlling myogenic precursor activity muscle regeneration vascularization. The disclosed reported by pharmacological activation selective agonist Yoda1 indicate potential impact channel regeneration, which is disrupted various muscular pathological states. All findings so far agree idea represent novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating disorders characterized an impairment tissue regenerative potential.

Language: Английский

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The Role of the Piezo1 Mechanosensitive Channel in the Musculoskeletal System

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6513 - 6513

Published: March 30, 2023

Since the recent discovery of mechanosensitive Piezo1 channels, many studies have addressed role channel in various physiological or even pathological processes different organs. Although number on their effects musculoskeletal system is constantly increasing, we are still far from a precise understanding. In this review, knowledge available so regarding summarized, reviewing results achieved field skeletal muscles, bones, joints and cartilage, tendons ligaments, as well intervertebral discs.

Language: Английский

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