GsMTx-4 combined with exercise improves skeletal muscle structure and motor function in rats with spinal cord injury DOI Creative Commons
Xin Zhang, Xinyu Liu, Qianxi Li

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0317683 - e0317683

Published: Jan. 22, 2025

Motor dysfunction and muscle atrophy are typical symptoms of patients with spinal cord injury (SCI). Exercise training is a conventional physical therapy after SCI, but exercise intervention alone may have limited efficacy in reducing secondary promoting nerve regeneration functional remodeling. Our previous research found that intramedullary pressure SCI one the key factors affecting prognosis. It has been reported GsMTx-4, specific blocker mechanosensitive ion channels Piezo1, can protect integrity neuromuscular junction promote regeneration, thus potential as therapeutic agent for SCI. In this study, we observed combined separate effect GsMTx-4 on structure soleus motor function rats At 42 days post-injury, compared rats, Basso–Beattie–Bresnahan score (P = 0.0007) Gait Symmetry 0.0002) were significantly improved combination therapy. On histology rat muscle, treatment increased wet weight ratio, fiber cross-sectional area acetylcholinesterase (all P<0.0001). tissue, neuron counts BDNF levels, reduced percentage TUNEL-positive cells physiology succinate dehydrogenase expression (P<0.0001), while α-glycerophosphate (P<0.0001) GDF8 protein 0.0008) decreased. Results indicate effectively improves histopathology enhancing function. This study was conducted animal models, it offers insights treatment, advancing understanding lower limb pathology post-SCI. Further needed clinical validation future.

Language: Английский

Piezo1 transforms mechanical stress into pro senescence signals and promotes osteoarthritis severity DOI
Yikai Liu, Zian Zhang, Jun Li

et al.

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 216, P. 111880 - 111880

Published: Oct. 13, 2023

Language: Английский

Citations

15
Low-load blood flow-restricted resistance exercise produces fiber type-independent hypertrophy and improves muscle functional capacity in older individuals DOI
Jakob Wang,

Anna-Maria Godsk Mogensen,

Frederik Thybo

et al.

Journal of Applied Physiology, Journal Year: 2023, Volume and Issue: 134(4), P. 1047 - 1062

Published: Feb. 24, 2023

Low-load blood flow-restricted resistance exercise (BFRRE) constitutes an effective means to produce skeletal muscle hypertrophy. Nonetheless, its applicability counteract the age-related decay at a cellular level, is not clear. Therefore, we investigated effect of BFRRE on fiber morphology, integrated protein synthesis, stem cells (MuSCs), myonuclear content, and functional capacity in healthy older individuals. Twenty-three participants with mean age 66 yr (56-75 yr) were randomized 6 wk supervised (3 sessions per week) or non-exercise control (CON). Biopsies collected from vastus lateralis before after intervention. Immunofluorescent microscopy was utilized assess type-specific cross-sectional area (CSA) as well MuSC content. Deuterium oxide orally administered throughout intervention period, enabling assessment myofibrillar connective tissue fractional synthesis rate (FSR). produced uniform ∼20% increases CSA both type I II fibers (P < 0.05). This occurred concomitantly improvements maximal strength strength-endurance but absence increased content addition. The observed hypertrophy mirrored by either FSR. In conclusion, proved stimulating growth function individuals, which advocates for use countermeasure deterioration mass function.NEW & NOTEWORTHY We provide novel insight, that little low-load produces pronounced type-independent hypertrophy, alongside across broad range Notably, since these results obtained modest volume very time-efficient manner, may represent potent strategy decay.

Language: Английский

Citations

14
The emerging role of Piezo1 in the musculoskeletal system and disease DOI Creative Commons
Lei Lei,

Zhenkang Wen,

Mingde Cao

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(10), P. 3963 - 3983

Published: Jan. 1, 2024

Piezo1, a mechanosensitive ion channel, has emerged as key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such lymphatic vessel development, axon growth, vascular immunoregulation, blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, homeostasis, recently attracted attention regarding the significance of Piezo1. This review aims to provide comprehensive summary current research on Piezo1 highlighting its impact bone formation, myogenesis, chondrogenesis, intervertebral disc tendon matrix cross-linking, physical activity. Additionally, we explore potential targeting therapeutic approach disorders, including osteoporosis, muscle atrophy, degeneration, osteoarthritis.

Language: Английский

Citations

5
Targeting miR-29 mitigates skeletal senescence and bolsters therapeutic potential of mesenchymal stromal cells DOI
Zhen Ding, Guixing Ma, Bo Zhou

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(8), P. 101665 - 101665

Published: Aug. 1, 2024

Language: Английский

Citations

5
The mechanosensitive ion channel PIEZO1 promotes satellite cell function in muscle regeneration DOI Creative Commons

Kotaro Hirano,

Masaki Tsuchiya, Akifumi Shiomi

et al.

Life Science Alliance, Journal Year: 2022, Volume and Issue: 6(2), P. e202201783 - e202201783

Published: Nov. 29, 2022

Muscle satellite cells (MuSCs), myogenic stem in skeletal muscles, play an essential role muscle regeneration. After injury, quiescent MuSCs are activated to enter the cell cycle and proliferate, thereby initiating regeneration; however, mechanisms that ensure successful MuSC division, including chromosome segregation, remain unclear. Here, we show PIEZO1, a calcium ion (Ca2+)-permeable cation channel by membrane tension, mediates spontaneous Ca2+ influx control regenerative function of MuSCs. Our genetic engineering approach mice revealed PIEZO1 is functionally expressed Piezo1 deletion these delays myofibre regeneration after injury. These results are, at least part, due mitotic defect Mechanistically, this phenotype caused impaired PIEZO1-Rho signalling during myogenesis. Thus, provide first concrete evidence bona fide mechanosensitive channel, promotes proliferation functions through precise division.

Language: Английский

Citations

19
Muscle stem cells get a new look: Dynamic cellular projections as sensors of the stem cell niche DOI
Robert S. Krauss, Allison P Kann

BioEssays, Journal Year: 2023, Volume and Issue: 45(5)

Published: March 14, 2023

Abstract Cellular mechanisms whereby quiescent stem cells sense tissue injury and transition to an activated state are largely unknown. Quiescent skeletal muscle (MuSCs, also called satellite cells) have elaborate, heterogeneous projections that rapidly retract in response injury. They may therefore act as direct sensors of their niche environment. Retraction is driven by a Rac‐to‐Rho GTPase activity switch promotes downstream MuSC activation events. These other observations lead several hypotheses: (1) morphologically dynamic at quiescence, providing surveillance function for damage; (2) projection dynamics regulated the relative balance Rac Rho activities promoted niche‐derived cues; (3) projections, particularly associated filopodia, damage via changes biomechanical properties and/or detection signaling cues released damaged myofibers; (4) nature results population MuSCs with functional properties. concepts extend types cells, well prove useful translational research settings.

Language: Английский

Citations

11
Three-Dimensional Matrix Stiffness Activates the Piezo1-AMPK-Autophagy Axis to Regulate the Cellular Osteogenic Differentiation DOI
Yanqiu Wu, Xinxin Xu, Fengyi Liu

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2023, Volume and Issue: 9(8), P. 4735 - 4746

Published: July 10, 2023

Extracellular matrix (ECM) stiffness is a key stimulus affecting cellular differentiation, and osteoblasts are also in three-dimensional (3D) stiff environment during the formation of bone tissues. However, it remains unclear how cells perceive mechanical stimuli translate them into intracellular signals to affect differentiation. Here, for first time, we constructed 3D culture by GelMA hydrogels with different amino substitution degrees found that Piezo1 expression was significantly stimulated high substitution; meanwhile, expressions osteogenic markers OSX, RUNX2, ALP were observably improved. Moreover, knockdown revealed significant reduction abovementioned markers. In addition, this biomimetic ECM, observed can be activated static conditions matrix, leading increase calcium content accompanied continuous change energy levels as ATP consumed More surprisingly, second messenger promoted activation AMP-activated protein kinase (AMPK) unc-51-like autophagy-activated 1 (ULK1) axis modestly modulated level autophagy, bringing more similar differentiated osteoblasts, increased metabolism consumption. Our study innovatively clarifies regulatory role mechanosensitive ion channel on differentiation verifies AMPK-ULK1 autophagy level. Collectively, our research develops understanding interaction mechanisms extracellular biomaterials from novel perspective provides theoretical basis regeneration design application.

Language: Английский

Citations

11
Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway DOI Creative Commons

Patcharapa Tragoonlugkana,

Chatchai Pruksapong,

Pawared Ontong

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 20, 2024

Abstract Cellular senescence plays a role in the development of aging-associated degenerative diseases. Cell therapy is recognized as candidate treatment for To achieve goal cell therapy, quality and good characteristics cells are concerned. expansion relies on two-dimensional culture, which leads to replicative expanded cells. This study aimed investigate effect culture surface modification using fibronectin (FN) vitronectin (VN) adipose-derived stem (ADSCs) during long-term expansion. Our results showed that ADSCs cultured FN VN coatings significantly enhanced adhesion, proliferation, slow progression cellular indicated by lower SA-β-gal activities decreased expression levels genes including p16, p21, p53. The upregulation integrin α5 αv influences phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), AKT proteins. upregulated MDM2 leading p53 degradation. Additionally, inhibition Nutlin-3a markedly elevated p21 expression, increased senescence, induced inflammatory molecules HMGB1 IL-6. understanding coating influencing ADSCs, especially characteristics, offers promising practical point cultivation future use cell-based therapies.

Language: Английский

Citations

4
Schisandrol B inhibits calcification of aortic valve by targeting p53 related inflammatory and senescence DOI Open Access
Xing Liu, Kan Wang, Qiang Zheng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117241 - 117241

Published: Aug. 6, 2024

Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact calcification not been reported. We investigated the effect of SolB hVICs. Transcriptome sequencing was used to analyze potential molecular pathways affected by treatment. The study also included an vivo murine model using wire injury surgery observe SolB's calcification. inhibited hVICs, reversing increase calcified nodule formation proteins. In model, significantly decreased peak velocity post-injury reduced fibrosis identified p53 signaling pathway as key target SolB, demonstrating role glue mouse double minute 2 (MDM2)-p53 interaction, thereby promoting ubiquitination degradation, which further p53-related senescence response. These results highlighted for CAVD via inhibiting revealed new mechanism provided insight theraputic CAVD.

Language: Английский

Citations

4
Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca2+ signaling DOI Creative Commons
Lingwei Huang, Yiren Jiao,

Hangbin Xia

et al.

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 48, P. 146 - 155

Published: Aug. 13, 2024

Language: Английский

Citations

4