Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Language: Английский

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Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 29, 2023

Abstract Osteoarthritis (OA) is a multifactorial and increasingly prevalent degenerative disease that affects the whole joint. The pathogenesis of OA poorly understood there lack therapeutic interventions to reverse pathological process this disease. Accumulating studies have shown overproduction reactive oxygen species (ROS) ROS-induced lipid peroxidation are involved in OA. 4-Hydroxy-2-nonenal (4-HNE) malondialdehyde (MDA) received considerable attention for their role cartilage degeneration subchondral bone remodeling during development. Ferroptosis form cell death characterized by control membrane recent suggested chondrocyte ferroptosis contributes progression. In review, we aim discuss peroxidation-derived 4-HNE MDA progression addition, potential controlling accumulation inhibiting discussed.

Language: Английский

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YAP/TAZ: Molecular pathway and disease therapy

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: Aug. 1, 2023

The Yes-associated protein and its transcriptional coactivator with PDZ-binding motif (YAP/TAZ) are two homologous coactivators that lie at the center of a key regulatory network Hippo, Wnt, GPCR, estrogen, mechanical, metabolism signaling. YAP/TAZ influences expressions downstream genes proteins as well enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, transdifferentiation fibroblasts into myofibroblasts. can also be regulated through epigenetic regulation posttranslational modifications. Consequently, function these mechanisms implicates pathogenesis metabolism-related diseases, atherosclerosis, fibrosis, delicate equilibrium between cancer progression organ regeneration. As such, there arises pressing need for thorough investigation clinical settings. In this paper, we aim to elucidate signaling pathways regulate explore YAP/TAZ-induce diseases their potential therapeutic interventions. Furthermore, summarize current studies investigating treatments targeting YAP/TAZ. We address limitations existing research on propose future directions research. conclusion, review aims provide fresh insights mediated by identify targets present innovative solutions overcome challenges associated

Language: Английский

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A static magnetic field enhances the repair of osteoarthritic cartilage by promoting the migration of stem cells and chondrogenesis

Journal of Orthopaedic Translation, Journal Year: 2023, Volume and Issue: 39, P. 43 - 54

Published: Jan. 7, 2023

To investigate the therapeutic effects of static magnetic field (SMF) and its regulatory mechanism in repair osteoarthritic cartilage.Fourteen-week-old female C57BL/6 mice were randomly divided into sham operation group osteoarthritis (OA) groups with without SMF application. was applied at 200 ​mT for two consecutive weeks. Changes knee cartilage examined by histomorphometry, chondrogenesis migration endogenous stem cells assessed. The expression SRY-related protein 9 (SOX9), Collagen type II (COL2), matrix metallopeptidase 13 (MMP13), stromal cell-derived factor 1/C-X-C chemokine receptor 4 (SDF-1/CXCR4), Piezo1 other genes evaluated, SMF's action tested using CXCR4 inhibitor, AMD3100, siRNA.SMF significantly decreased OARSI scores after induction OA. beneficial to elevating SOX9. In OA mouse model, an increase MMP13 a decrease COL2 led destruction extracellular matrix, which suppressed SMF. promoted cartilage-derived stem/progenitor bone marrow-derived mesenchymal (MSCs). It increased SDF-1 CXCR4, while inhibitor application siRNA inhibited SMF-induced CXCR4.SMF enhanced improved matrices. activated Piezo1-mediated SDF-1/CXCR4 axis cells. Collectively, it attenuated pathological progression mice.The findings this study provided convincing evidence that could enhance improve symptoms, suggesting have clinical value treatment

Language: Английский

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The role of lipid metabolism in osteoporosis: Clinical implication and cellular mechanism

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(4), P. 101122 - 101122

Published: Sept. 21, 2023

In recent years, researchers have become focused on the relationship between lipids and bone metabolism balance. Moreover, many diseases related to lipid disorders, such as nonalcoholic fatty liver disease, atherosclerosis, obesity, menopause, are associated with osteoporotic phenotypes. It has been clinically observed in humans that these disorders promote changes osteoporosis-related indicators mineral density mass. Furthermore, similar phenotype were high-fat high-cholesterol-induced animal models. Abnormal (such increased oxidized elevated plasma cholesterol) affects microenvironment homeostasis via cross-organ communication, promoting differentiation of mesenchymal stem cells adipocytes, inhibiting commitment towards osteoblasts. disturbances affect balance by secretion cytokines receptor activator nuclear factor-kappa B ligand osteoblasts stimulating osteoclasts. Conclusively, this review addresses possible link osteoporosis elucidates potential modulatory mechanisms signaling pathways which We also summarize approaches prospects intervening for treatment.

Language: Английский

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Substrate stiffness modulates osteogenic and adipogenic differentiation of osteosarcoma through PIEZO1 mediated signaling pathway

Cellular Signalling, Journal Year: 2025, Volume and Issue: 127, P. 111601 - 111601

Published: Jan. 9, 2025

Language: Английский

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Mechanosensitive Piezo1 protein as a novel regulator in macrophages and macrophage-mediated inflammatory diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 2, 2023

Macrophages are the most important innate immune cells in humans. They almost ubiquitous peripheral tissues with a large variety of different mechanical milieus. Therefore, it is not inconceivable that stimuli have effects on macrophages. Emerging as key molecular detectors stress, function Piezo channels macrophages becoming attractive. In this review, we addressed architecture, activation mechanisms, biological functions, and pharmacological regulation Piezo1 channel review research advancements functions macrophage-mediated inflammatory diseases well potential mechanisms involved.

Language: Английский

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The periodontal ligament, temperature‐sensitive ion channels TRPV1–4, and the mechanosensitive ion channels Piezo1 and 2: A Nobel connection

Journal of Periodontal Research, Journal Year: 2023, Volume and Issue: 58(4), P. 687 - 696

Published: June 8, 2023

Abstract Teeth are subject to a variety of mechanical forces and vectors. The periodontal ligament (PDL), fibrous tissue that connects the cementum tooth bony socket, plays decisive role in transmitting force alveolar bone via Sharpey fibers, transforming converting these into biological signals. This interaction effects significant osteoblastic osteoclastic responses autocrine proliferative paracrine responses. Recent discoveries receptors for temperature touch by Nobel laureates David Julius Ardem Patapoutian, respectively have profound impact on orthodontics. Transient receptor vanilloid channel 1 (TRPV1), initially described as temperature, has been proposed participate sensing force. TRPV4, another ion receptor, perceives tensile well thermal chemical stimuli. Piezo1 2, classic touch, addition aforementioned receptors, similarly PDL‐derived cells. In this text, we review temperature‐sensitive channels mechanosensitive their function influence orthodontic treatment.

Language: Английский

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Regulation of bone homeostasis: signaling pathways and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 24, 2024

As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both formation by osteoblasts and resorption osteoclasts constitute reconstruction homeostasis. The equilibrium of homeostasis governed many complicated signaling pathways that weave together to form an intricate network. These coordinate the meticulous processes resorption, ensuring structural integrity vitality skeletal system. Dysregulation homeostatic regulatory network contributes development progression diseases. Significantly, imbalanced further disrupts triggers cascade reaction exacerbates disease engenders deleterious cycle. Here, we summarize influence on homeostasis, elucidating interplay crosstalk among them. Additionally, review mechanisms underpinning imbalances across diverse landscapes, highlighting current prospective therapeutic targets clinical drugs. We hope this will contribute holistic understanding molecular sustaining which are promising research shed light targeted

Language: Английский

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Biomechanical Effects of Mechanical Stress on Cells Involved in Fracture Healing

Orthopaedic Surgery, Journal Year: 2024, Volume and Issue: 16(4), P. 811 - 820

Published: March 4, 2024

Fracture healing is a complex staged repair process in which the mechanical environment plays key role. Bone tissue very sensitive to stress stimuli, and literature suggests that appropriate can promote fracture by altering cellular function. However, coupled involving multiple cell types balance limit each other ensure proper healing. The main cells function during different stages of are different, molecular mechanisms required also different. Most previous studies have used single stimulus on individual mechanosensitive cells, there no relatively uniform standard for size frequency stress. Analyzing underlying effects stimulation metabolic regulation signaling pathways such as bone marrow mesenchymal stem (BMSCs), osteoblasts, chondrocytes, osteoclasts currently challenging research hotspot. Grasping how affects at biology level contribute refined management Therefore, this review, we summarize relevant describe associated with healing, their possible pathways, treatment fractures further development regenerative medicine.

Language: Английский

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