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Keywords = mechanoregulation

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15 pages, 7207 KB  
Article
Collagen Fiber Maturity and Architecture in MVP-Associated Fibrosis Quantified by Digital Pathology
by Ranan Phookan, Jordan E. Morningstar, Brian Loizzi, Antonia Van Kampen, Cortney Gensemer, Maja-Theresa Dieterlen, Ricardo Spampinato, Louis Petitjean, Mathieu Petitjean, Taylor Petrucci, Roman Fenner, Jake Griner, Kathryn Byerly, Robert A. Levine, Michael A. Borger and Russell A. Norris
Cells 2025, 14(19), 1536; https://doi.org/10.3390/cells14191536 - 30 Sep 2025
Abstract
Recent evidence demonstrates that mitral valve prolapse (MVP) increases mechanical stress on the subvalvular apparatus and is linked to regional myocardial fibrosis and life-threatening ventricular arrhythmias. However, current surgical guidelines do not account for the extent of myocardial fibrosis or the severity of [...] Read more.
Recent evidence demonstrates that mitral valve prolapse (MVP) increases mechanical stress on the subvalvular apparatus and is linked to regional myocardial fibrosis and life-threatening ventricular arrhythmias. However, current surgical guidelines do not account for the extent of myocardial fibrosis or the severity of leaflet involvement, both key features of arrhythmogenic MVP. To address this gap, we conducted histopathological analysis of endomyocardial biopsies from patients with MVP and regionalized myocardial fibrosis (n = 6) who underwent mitral valve repair. Using digital pathology-based quantitative image analysis (QIA), we found that fibrosis in peri-papillary biopsies exhibited a significantly higher Morphometric Composite Score compared with remote biopsies (5.68 ± 0.69 vs. 3.71 ± 0.49, p = 0.042), reflecting larger, more branched, and more assembled collagen fibers, indicative of a mature and persistent fibrotic phenotype. These findings suggest that myocardial scarring in MVP is well-established by the time of surgery and underscore the potential value of earlier surgical intervention to reduce the risk of arrhythmia and preserve post-operative left ventricular function. Full article
17 pages, 6509 KB  
Article
Mechanoregulation of Osteoclastogenesis-Inducing Potentials of Fibrosarcoma Cell Line by Substrate Stiffness
by Watcharaphol Tiskratok, Masahiro Yamada, Jun Watanabe, Qu Pengyu, Tsuyoshi Kimura and Hiroshi Egusa
Int. J. Mol. Sci. 2023, 24(10), 8959; https://doi.org/10.3390/ijms24108959 - 18 May 2023
Cited by 4 | Viewed by 2574
Abstract
A micro-physiological system is generally fabricated using soft materials, such as polydimethylsiloxane silicone (PDMS), and seeks an inflammatory osteolysis model for osteoimmunological research as one of the development needs. Microenvironmental stiffness regulates various cellular functions via mechanotransduction. Controlling culture substrate stiffness may help [...] Read more.
A micro-physiological system is generally fabricated using soft materials, such as polydimethylsiloxane silicone (PDMS), and seeks an inflammatory osteolysis model for osteoimmunological research as one of the development needs. Microenvironmental stiffness regulates various cellular functions via mechanotransduction. Controlling culture substrate stiffness may help spatially coordinate the supply of osteoclastogenesis-inducing factors from immortalized cell lines, such as mouse fibrosarcoma L929 cells, within the system. Herein, we aimed to determine the effects of substrate stiffness on the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction. L929 cells showed increased expression of osteoclastogenesis-inducing factors when cultured on type I collagen-coated PDMS substrates with soft stiffness, approximating that of soft tissue sarcomas, regardless of the addition of lipopolysaccharide to augment proinflammatory reactions. Supernatants of L929 cells cultured on soft PDMS substrates promoted osteoclast differentiation of the mouse osteoclast precursor RAW 264.7 by stimulating the expression of osteoclastogenesis-related gene markers and tartrate-resistant acid phosphatase activity. The soft PDMS substrate inhibited the nuclear translocation of YES-associated proteins in L929 cells without reducing cell attachment. However, the hard PDMS substrate hardly affected the cellular response of the L929 cells. Our results showed that PDMS substrate stiffness tuned the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction. Full article
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19 pages, 6857 KB  
Article
Prediction of Bone Healing around Dental Implants in Various Boundary Conditions by Deep Learning Network
by Pei-Ching Kung, Chia-Wei Hsu, An-Cheng Yang, Nan-Yow Chen and Nien-Ti Tsou
Int. J. Mol. Sci. 2023, 24(3), 1948; https://doi.org/10.3390/ijms24031948 - 18 Jan 2023
Cited by 9 | Viewed by 3095
Abstract
Tissue differentiation varies based on patients’ conditions, such as occlusal force and bone properties. Thus, the design of the implants needs to take these conditions into account to improve osseointegration. However, the efficiency of the design procedure is typically not satisfactory and needs [...] Read more.
Tissue differentiation varies based on patients’ conditions, such as occlusal force and bone properties. Thus, the design of the implants needs to take these conditions into account to improve osseointegration. However, the efficiency of the design procedure is typically not satisfactory and needs to be significantly improved. Thus, a deep learning network (DLN) is proposed in this study. A data-driven DLN consisting of U-net, ANN, and random forest models was implemented. It serves as a surrogate for finite element analysis and the mechano-regulation algorithm. The datasets include the history of tissue differentiation throughout 35 days with various levels of occlusal force and bone properties. The accuracy of day-by-day tissue differentiation prediction in the testing dataset was 82%, and the AUC value of the five tissue phenotypes (fibrous tissue, cartilage, immature bone, mature bone, and resorption) was above 0.86, showing a high prediction accuracy. The proposed DLN model showed the robustness for surrogating the complex, time-dependent calculations. The results can serve as a design guideline for dental implants. Full article
(This article belongs to the Special Issue Biological Cues for Tissue Regeneration and Bioactive Materials)
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13 pages, 3115 KB  
Article
Reduced Cell–ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation
by Kshitij Amar, Sanjoy Saha, Avishek Debnath, Chun Hung Weng, Arpan Roy, Kyu Young Han and Farhan Chowdhury
Cells 2023, 12(2), 326; https://doi.org/10.3390/cells12020326 - 15 Jan 2023
Cited by 2 | Viewed by 3963
Abstract
Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect [...] Read more.
Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect during differentiation is even more pronounced. While past studies implicated variations in signaling pathways to be the root cause of heterogeneity, the biophysical aspects of differentiation have not been thoroughly considered. Here, we demonstrate that the heterogeneity of EpiSC differentiation arises from differences in the colony size and varying degrees of interactions between cells within the colonies and the ECM. Confocal imaging demonstrates that cells in the colony periphery established good contact with the surface while the cells in the colony center were separated by an average of 1–2 µm from the surface. Traction force measurements of the cells within the EpiSC colonies show that peripheral cells generate large tractions while the colony center cells do not. A finite element modeling of EpiSC colonies shows that tractions generated by the cells at the colony periphery lift off the colony center preventing the colony center from undergoing differentiation. Together, our results demonstrate a biophysical regulation of heterogeneous EpiSC colony differentiation. Full article
(This article belongs to the Special Issue Mechanics of Stem Cells in Regenerative Medicine)
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26 pages, 1555 KB  
Review
Mechanotransduction in Skin Inflammation
by Maria S. Shutova and Wolf-Henning Boehncke
Cells 2022, 11(13), 2026; https://doi.org/10.3390/cells11132026 - 25 Jun 2022
Cited by 29 | Viewed by 7948
Abstract
In the process of mechanotransduction, the cells in the body perceive and interpret mechanical stimuli to maintain tissue homeostasis and respond to the environmental changes. Increasing evidence points towards dysregulated mechanotransduction as a pathologically relevant factor in human diseases, including inflammatory conditions. Skin [...] Read more.
In the process of mechanotransduction, the cells in the body perceive and interpret mechanical stimuli to maintain tissue homeostasis and respond to the environmental changes. Increasing evidence points towards dysregulated mechanotransduction as a pathologically relevant factor in human diseases, including inflammatory conditions. Skin is the organ that constantly undergoes considerable mechanical stresses, and the ability of mechanical factors to provoke inflammatory processes in the skin has long been known, with the Koebner phenomenon being an example. However, the molecular mechanisms and key factors linking mechanotransduction and cutaneous inflammation remain understudied. In this review, we outline the key players in the tissue’s mechanical homeostasis, the available data, and the gaps in our current understanding of their aberrant regulation in chronic cutaneous inflammation. We mainly focus on psoriasis as one of the most studied skin inflammatory diseases; we also discuss mechanotransduction in the context of skin fibrosis as a result of chronic inflammation. Even though the role of mechanotransduction in inflammation of the simple epithelia of internal organs is being actively studied, we conclude that the mechanoregulation in the stratified epidermis of the skin requires more attention in future translational research. Full article
(This article belongs to the Special Issue Cell-Cell Interactions and Cell Adhesion Signaling in Disease States)
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17 pages, 2348 KB  
Article
A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
by Sinan Şen, Christopher J. Lux and Ralf Erber
Int. J. Mol. Sci. 2021, 22(15), 8297; https://doi.org/10.3390/ijms22158297 - 2 Aug 2021
Cited by 18 | Viewed by 3368
Abstract
Background: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal guidance molecules have been implicated in the [...] Read more.
Background: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal guidance molecules have been implicated in the regulation of bone remodeling. Amongst them, Semaphorin 3A is particular interesting as it concurrently induces osteoblast differentiation and disturbs osteoclast differentiation. Methods: Mechano-regulation of Sema3A and its receptors PlexinA1 and Neuropilin (RT-qPCR, WB) was evaluated by applying compressive and tension forces to primary human periodontal fibroblasts (hPDLF) and alveolar bone osteoblasts (hOB). The association of the transcription factor Osterix (SP7) and SEMA3A was studied by RT-qPCR. Mechanisms involved in SEMA3A-mediated osteoblast differentiation were assessed by Rac1GTPase pull-downs, β-catenin expression analyses (RT-qPCR) and nuclear translocation assays (IF). Osteogenic markers were analyzed by RT-qPCR. Results: SEMA3A, PLXNA1 and NRP1 were differentially regulated by tension or compressive forces in hPDLF. Osterix (SP7) displayed the same pattern of regulation. Recombinant Sema3A induced the activation of Rac1GTPase, the nuclear translocation of β-catenin and the expression of osteogenic marker genes. Conclusion: Sema3A, its receptors and Osterix are regulated by mechanical forces in hPDLF. SEMA3A upregulation was associated with Osterix (SP7) modulation. Sema3A-enhanced osteogenic marker gene expression in hOB might be dependent on a pathway involving Rac1GTPase and β-catenin. Thus, Semaphorin 3A might contribute to bone remodeling during induced tooth movement. Full article
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20 pages, 3438 KB  
Article
Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis
by Matthew Goelzer, Amel Dudakovic, Melis Olcum, Buer Sen, Engin Ozcivici, Janet Rubin, Andre J. van Wijnen and Gunes Uzer
Int. J. Mol. Sci. 2021, 22(12), 6580; https://doi.org/10.3390/ijms22126580 - 19 Jun 2021
Cited by 16 | Viewed by 4679
Abstract
Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein [...] Read more.
Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C. Full article
(This article belongs to the Special Issue Nuclear Envelope Proteins 2.0)
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19 pages, 17974 KB  
Article
Heparan Sulfate Deficiency in Cartilage: Enhanced BMP-Sensitivity, Proteoglycan Production and an Anti-Apoptotic Expression Signature after Loading
by Matthias Gerstner, Ann-Christine Severmann, Safak Chasan, Andrea Vortkamp and Wiltrud Richter
Int. J. Mol. Sci. 2021, 22(7), 3726; https://doi.org/10.3390/ijms22073726 - 2 Apr 2021
Cited by 6 | Viewed by 4381
Abstract
Osteoarthritis (OA) represents one major cause of disability worldwide still evading efficient pharmacological or cellular therapies. Severe degeneration of extracellular cartilage matrix precedes the loss of mobility and disabling pain perception in affected joints. Recent studies showed that a reduced heparan sulfate (HS) [...] Read more.
Osteoarthritis (OA) represents one major cause of disability worldwide still evading efficient pharmacological or cellular therapies. Severe degeneration of extracellular cartilage matrix precedes the loss of mobility and disabling pain perception in affected joints. Recent studies showed that a reduced heparan sulfate (HS) content protects cartilage from degradation in OA-animal models of joint destabilization but the underlying mechanisms remained unclear. We aimed to clarify whether low HS-content alters the mechano-response of chondrocytes and to uncover pathways relevant for HS-related chondro-protection in response to loading. Tissue-engineered cartilage with HS-deficiency was generated from rib chondrocytes of mice carrying a hypomorphic allele of Exostosin 1 (Ext1), one of the main HS-synthesizing enzymes, and wildtype (WT) littermate controls. Engineered cartilage matured for 2 weeks was exposed to cyclic unconfined compression in a bioreactor. The molecular loading response was determined by transcriptome profiling, bioinformatic data processing, and qPCR. HS-deficient chondrocytes expressed 3–6% of WT Ext1-mRNA levels. Both groups similarly raised Sox9, Col2a1 and Acan levels during maturation. However, HS-deficient chondrocytes synthesized and deposited 50% more GAG/DNA. TGFβ and FGF2-sensitivity of Ext1gt/gt chondrocytes was similar to WT cells but their response to BMP-stimulation was enhanced. Loading induced similar activation of mechano-sensitive ERK and P38-signaling in WT and HS-reduced chondrocytes. Transcriptome analysis reflected regulation of cell migration as major load-induced biological process with similar stimulation of common (Fosl1, Itgα5, Timp1, and Ngf) as well as novel mechano-regulated genes (Inhba and Dhrs9). Remarkably, only Ext1-hypomorphic cartilage responded to loading by an expression signature of negative regulation of apoptosis with pro-apoptotic Bnip3 being selectively down-regulated. HS-deficiency enhanced BMP-sensitivity, GAG-production and fostered an anti-apoptotic expression signature after loading, all of which may protect cartilage from load-induced erosion. Full article
(This article belongs to the Special Issue Extracellular Matrix in Development and Disease 3.0)
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20 pages, 6989 KB  
Review
Perlecan in Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation and Mechanoregulation of Load-Bearing Connective Tissues
by Farshid Guilak, Anthony J. Hayes and James Melrose
Int. J. Mol. Sci. 2021, 22(5), 2716; https://doi.org/10.3390/ijms22052716 - 8 Mar 2021
Cited by 51 | Viewed by 6141
Abstract
In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. [...] Read more.
In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. Pericellular perlecan interacts with collagen VI and XI to define and stabilize this matrix compartment which has a strategic position facilitating two-way cell-matrix communication between the cell and its wider extracellular matrix. Cues from the extracellular matrix are fed through this pericellular matrix back to the chondrocyte, allowing it to perceive and respond to subtle microenvironmental changes to regulate tissue homeostasis. Thus perlecan plays a key regulatory role in chondrocyte metabolism, and in chondrocyte differentiation. Perlecan acts as a transport proteoglycan carrying poorly soluble, lipid-modified proteins such as the Wnt or Hedgehog families facilitating the establishment of morphogen gradients that drive tissue morphogenesis. Cell surface perlecan on endothelial cells or osteocytes acts as a flow sensor in blood and the lacunar canalicular fluid providing feedback cues to smooth muscle cells regulating vascular tone and blood pressure, and the regulation of bone metabolism by osteocytes highlighting perlecan’s multifaceted roles in load-bearing connective tissues. Full article
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15 pages, 3587 KB  
Article
A Hybrid Model for Predicting Bone Healing around Dental Implants
by Pei-Ching Kung, Shih-Shun Chien and Nien-Ti Tsou
Materials 2020, 13(12), 2858; https://doi.org/10.3390/ma13122858 - 25 Jun 2020
Cited by 6 | Viewed by 4016
Abstract
Background: The effect of the short-term bone healing process is typically neglected in numerical models of bone remodeling for dental implants. In this study, a hybrid two-step algorithm was proposed to enable a more accurate prediction for the performance of dental implants. Methods: [...] Read more.
Background: The effect of the short-term bone healing process is typically neglected in numerical models of bone remodeling for dental implants. In this study, a hybrid two-step algorithm was proposed to enable a more accurate prediction for the performance of dental implants. Methods: A mechano-regulation algorithm was firstly used to simulate the tissue differentiation around a dental implant during the short-term bone healing. Then, the result was used as the initial state of the bone remodeling model to simulate the long-term healing of the bones. The algorithm was implemented by a 3D finite element model. Results: The current hybrid model reproduced several features which were discovered in the experiments, such as stress shielding effect, high strength bone connective tissue bands, and marginal bone loss. A reasonable location of bone resorptions and the stability of the dental implant is predicted, compared with those predicted by the conventional bone remodeling model. Conclusions: The hybrid model developed here predicted bone healing processes around dental implants more accurately. It can be used to study bone healing before implantation surgery and assist in the customization of dental implants. Full article
(This article belongs to the Special Issue Dental Implant Materials 2019)
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13 pages, 3149 KB  
Communication
A Toolbox for Organelle Mechanobiology Research—Current Needs and Challenges
by Qian Feng, Sung Sik Lee and Benoît Kornmann
Micromachines 2019, 10(8), 538; https://doi.org/10.3390/mi10080538 - 16 Aug 2019
Cited by 11 | Viewed by 5873
Abstract
Mechanobiology studies from the last decades have brought significant insights into many domains of biological research, from development to cellular signaling. However, mechano-regulation of subcellular components, especially membranous organelles, are only beginning to be unraveled. In this paper, we take mitochondrial mechanobiology as [...] Read more.
Mechanobiology studies from the last decades have brought significant insights into many domains of biological research, from development to cellular signaling. However, mechano-regulation of subcellular components, especially membranous organelles, are only beginning to be unraveled. In this paper, we take mitochondrial mechanobiology as an example to discuss recent advances and current technical challenges in this field. In addition, we discuss the needs for future toolbox development for mechanobiological research of intracellular organelles. Full article
(This article belongs to the Special Issue Microfluidics for Soft Matter and Mechanobiology, Volume I)
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16 pages, 2087 KB  
Perspective
Mechanoregulation of Bone Remodeling and Healing as Inspiration for Self-Repair in Materials
by Richard Weinkamer, Christoph Eberl and Peter Fratzl
Biomimetics 2019, 4(3), 46; https://doi.org/10.3390/biomimetics4030046 - 9 Jul 2019
Cited by 21 | Viewed by 10172
Abstract
The material bone has attracted the attention of material scientists due to its fracture resistance and ability to self-repair. A mechanoregulated exchange of damaged bone using newly synthesized material avoids the accumulation of fatigue damage. This remodeling process is also the basis for [...] Read more.
The material bone has attracted the attention of material scientists due to its fracture resistance and ability to self-repair. A mechanoregulated exchange of damaged bone using newly synthesized material avoids the accumulation of fatigue damage. This remodeling process is also the basis for structural adaptation to common loading conditions, thereby reducing the probability of material failure. In the case of fracture, an initial step of tissue formation is followed by a mechanobiological controlled restoration of the pre-fracture state. The present perspective focuses on these mechanobiological aspects of bone remodeling and healing. Specifically, the role of the control function is considered, which describes mechanoregulation as a link between mechanical stimulation and the local response of the material through changes in structure or material properties. Mechanical forces propagate over large distances leading to a complex non-local feedback between mechanical stimulation and material response. To better understand such phenomena, computer models are often employed. As expected from control theory, negative and positive feedback loops lead to entirely different time evolutions, corresponding to stable and unstable states of the material system. After some background information about bone remodeling and healing, we describe a few representative models, the corresponding control functions, and their consequences. The results are then discussed with respect to the potential design of synthetic materials with specific self-repair properties. Full article
(This article belongs to the Special Issue Biogenic and Bioinspired Self-Healing Materials)
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22 pages, 2472 KB  
Review
Deciphering Nuclear Mechanobiology in Laminopathy
by Jungwon Hah and Dong-Hwee Kim
Cells 2019, 8(3), 231; https://doi.org/10.3390/cells8030231 - 11 Mar 2019
Cited by 32 | Viewed by 9539
Abstract
Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation, which encompasses mechanosensing and mechanotransduction. The nuclear lamina underlying the inner nuclear membrane not only maintains the structural integrity, but also connects [...] Read more.
Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation, which encompasses mechanosensing and mechanotransduction. The nuclear lamina underlying the inner nuclear membrane not only maintains the structural integrity, but also connects the cytoskeleton to the nuclear envelope. Lamin mutations, therefore, dysregulate the nuclear response, resulting in abnormal mechanoregulations, and ultimately, disease progression. Impaired mechanoregulations even induce malfunction in nuclear positioning, cell migration, mechanosensation, as well as differentiation. To know how to overcome laminopathies, we need to understand the mechanisms of laminopathies in a mechanobiological way. Recently, emerging studies have demonstrated the varying defects from lamin mutation in cellular homeostasis within mechanical surroundings. Therefore, this review summarizes recent findings highlighting the role of lamins, the architecture of nuclear lamina, and their disease relevance in the context of nuclear mechanobiology. We will also provide an overview of the differentiation of cellular mechanics in laminopathy. Full article
(This article belongs to the Collection Lamins and Laminopathies)
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24 pages, 3834 KB  
Article
Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages
by Dominique Muschter, Anna-Sophie Beiderbeck, Tanja Späth, Christian Kirschneck, Agnes Schröder and Susanne Grässel
Int. J. Mol. Sci. 2019, 20(3), 503; https://doi.org/10.3390/ijms20030503 - 24 Jan 2019
Cited by 17 | Viewed by 5675
Abstract
This study aimed to analyze if the sensory neuropeptide SP (SP) and the neurokinin receptor 1 (NK1R) are involved in macrophage mechano-transduction, similar to chondrocytes, and if alpha-calcitonin gene-related peptide (αCGRP) and the CGRP receptor (CRLR/Ramp1) show comparable activity. Murine RAW264.7 macrophages were [...] Read more.
This study aimed to analyze if the sensory neuropeptide SP (SP) and the neurokinin receptor 1 (NK1R) are involved in macrophage mechano-transduction, similar to chondrocytes, and if alpha-calcitonin gene-related peptide (αCGRP) and the CGRP receptor (CRLR/Ramp1) show comparable activity. Murine RAW264.7 macrophages were subjected to a cyclic stretch for 1–3 days and 4 h/day. Loading and neuropeptide effects were analyzed for gene and protein expression of neuropeptides and their receptors, adhesion, apoptosis, proliferation and ROS activity. Murine bone marrow-derived macrophages (BMM) were isolated after surgical osteoarthritis (OA) induction and proliferation, apoptosis and osteoclastogenesis were analyzed in response to loading. Loading induced NK1R and CRLR/Ramp1 gene expression and altered protein expression in RAW264.7 macrophages. SP protein and mRNA level decreased after loading whereas αCGRP mRNA expression was stabilized. SP reduced adhesion in loaded RAW264.7 macrophages and both neuropeptides initially increased the ROS activity followed by a time-dependent suppression. OA induction sensitized BMM to caspase 3/7 mediated apoptosis after loading. Both sensory neuropeptides, SP and αCGRP, and their receptors are involved in murine macrophage mechano-transduction affecting neuropeptide impact on adhesion and ROS activity. OA induction altered BMM apoptosis in response to loading indicate that OA-associated biomechanical alterations might affect the macrophage population. Full article
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