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https://www.readbyqxmd.com/read/28340249/orthodontic-strain-affects-the-hippo-pathway-effector-yap-concomitant-with-proliferation-in-human-periodontal-ligament-fibroblasts
#1
Diana Huelter-Hassler, Pascal Tomakidi, Thorsten Steinberg, Britta A Jung
Objectives: During orthodontic tooth movement (OTM), human periodontal ligament fibroblasts (hPDLFs) sense, and respond to mechanical forces. Since the molecular constituents involved in these processes are not fully elucidated, the objective of the present study was to identify further key molecules of the cellular strain response. Materials and Methods: Primary hPDLFs were strained with a static equiaxial strain of 2.5 per cent for 15 minutes, 1 hour, 6 hours, and 24 hours...
March 17, 2017: European Journal of Orthodontics
https://www.readbyqxmd.com/read/28339567/role-of-biomechanical-forces-in-hyperfiltration-mediated-glomerular-injury-in-congenital-anomalies-of-the-kidney-and-urinary-tract
#2
Tarak Srivastava, Ganesh Thiagarajan, Uri S Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T McCarthy, Virginia J Savin, Mukut Sharma
Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear...
January 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28322825/dissection-of-mechanoresponse-elements-in-promoter-sites-of-the-mechanoresponsive-cyr61-gene
#3
Lothar Seefried, Sigrid Mueller-Deubert, Melanie Krug, Almoatazbellah Youssef, Norbert Schuetze, Anita Ignatius, Franz Jakob, Regina Ebert
Mechanotransduction is important for mesenchymal regeneration and differentiation. Exaggerated high or very low impact yields pathological outcome resulting in fracture or tissue atrophy. Pathological strain in animal models was described but tools to dissect the respective stimuli and downstream pathways are limited. We expand the analytical tools to describe DNA strain response elements in a reporter gene approach. Deletion constructs of the human cysteine-rich protein 61 (CYR61) promoter were cloned into luciferase vectors and stably transfected into human telomerase-immortalized mesenchymal stem cells (hMSC-TERT)...
March 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28322464/cathepsin-k-controls-cortical-bone-formation-by-degrading-periostin
#4
Nicolas Bonnet, Julia Brun, Jean-Charles Rousseau, Le T Duong, Serge L Ferrari
While inhibitors of bone resorption concomitantly reduce bone formation because of the coupling between osteoclasts and osteoblasts, inhibition or deletion of cathepsin k (CatK) stimulates bone formation despite decreasing resorption. The molecular mechanisms responsible for this increase in bone formation, particularly at periosteal surfaces where osteoclasts are relatively poor, remain unclear. Here we show that CatK pharmacological inhibition or deletion (Ctsk(-/-) mice) potentiates mechanotransduction signals mediating cortical bone formation...
March 21, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28303387/caveolar-remodeling-is-a-critical-mechanotransduction-mechanism-of-the-stretch-induced-l-type-ca-2-channel-activation-in-vascular-myocytes
#5
Sang Woong Park, Kyung Chul Shin, Hyun Ji Park, Soon-Kyu Yoou, Jin-Yeon Park, Young-Sun Kang, Dong Jun Sung, Jae Gon Kim, Seung Hwa Park, BoKyung Kim, Hana Cho, Young Min Bae
Activation of L-type voltage-dependent Ca(2+) channels (VDCCL) by membrane stretch contributes to many biological responses such as myogenic contraction of arteries. However, mechanism for the stretch-induced VDCCL activation is unclear. In this study, we examined the hypothesis that caveolar remodeling and its related signaling cascade contribute to the stretch-induced activation of VDCCL in rat mesenteric arterial smooth muscle cells. The VDCCL currents were recorded with nystatin-perforated or with conventional whole-cell patch-clamp technique...
March 16, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28302906/distinct-focal-adhesion-protein-modules-control-different-aspects-of-mechanotransduction
#6
Ben Stutchbury, Paul Atherton, Ricky Tsang, De-Yao Wang, Christoph Ballestrem
Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. Using fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP), we found that the mobility of core FA proteins correlates with protein function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting they are involved in sensing the rigidity of the extracellular environment...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28290481/identification-of-elongated-primary-cilia-with-impaired-mechanotransduction-in-idiopathic-scoliosis-patients
#7
Niaz Oliazadeh, Kristen F Gorman, Robert Eveleigh, Guillaume Bourque, Alain Moreau
The primary cilium is an outward projecting antenna-like organelle with an important role in bone mechanotransduction. The capacity to sense mechanical stimuli can affect important cellular and molecular aspects of bone tissue. Idiopathic scoliosis (IS) is a complex pediatric disease of unknown cause, defined by abnormal spinal curvatures. We demonstrate significant elongation of primary cilia in IS patient bone cells. In response to mechanical stimulation, these IS cells differentially express osteogenic factors, mechanosensitive genes, and signaling genes...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289092/ampk-negatively-regulates-tensin-dependent-integrin-activity
#8
Maria Georgiadou, Johanna Lilja, Guillaume Jacquemet, Camilo Guzmán, Maria Rafaeva, Charlotte Alibert, Yan Yan, Pranshu Sahgal, Martina Lerche, Jean-Baptiste Manneville, Tomi P Mäkelä, Johanna Ivaska
Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a β1-integrin inhibitor in fibroblasts. Loss of AMPK promotes β1-integrin activity, the formation of centrally located active β1-integrin- and tensin-rich mature fibrillar adhesions, and cell spreading...
March 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28280468/rok-and-arteriolar-myogenic-tone-generation-molecular-evidence-in-health-and-disease
#9
REVIEW
Ahmed F El-Yazbi, Khaled S Abd-Elrahman
The myogenic response is an inherent property of resistance arteries that warrants a relatively constant blood flow in response to changes in perfusion pressure and protect delicate organs from vascular insufficiencies and excessive blood flow. This fundamental phenomenon has been extensively studied aiming to elucidate the underlying mechanisms triggering smooth muscle contraction in response to intraluminal pressure elevation, particularly, Rho-associated kinase (ROK)-mediated Ca(2+)-independent mechanisms...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28277000/the-development-of-polymeric-biomaterials-inspired-by-the-extracellular-matrix
#10
Daniel E Heath, Stuart L Cooper
The field of biomaterials science has exhibited astounding growth during the last half century. This growth can be attributed to a more thorough understanding of cellular behaviours, new mechanistic insights into cell-materials interactions, advances in polymer synthesis, and the development of innovative fabrication techniques. This progress has enabled biomaterials to transition from materials that fill in for damaged or diseased tissues to implants that actively work with biology to aid in the healing process...
February 28, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28273460/agrin-as-a-mechanotransduction-signal-regulating-yap-through-the-hippo-pathway
#11
Sayan Chakraborty, Kizito Njah, Ajaybabu V Pobbati, Ying Bena Lim, Anandhkumar Raju, Manikandan Lakshmanan, Vinay Tergaonkar, Chwee Teck Lim, Wanjin Hong
The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28263185/laminar-flow-downregulates-notch-activity-to-promote-lymphatic-sprouting
#12
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Jaehyuk Yoo, Esak Lee, Mingu Hong, Sunju Lee, Hiroaki Ishida, James Burford, Janos Peti-Peterdi, Ralf H Adams, Sonal Srikanth, Yousang Gwack, Christopher S Chen, Hans J Vogel, Chester J Koh, Alex K Wong, Young-Kwon Hong
The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity...
March 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28262745/a-biomimetic-gelatin-based-platform-elicits-a-pro-differentiation-effect-on-podocytes-through-mechanotransduction
#13
Mufeng Hu, Evren U Azeloglu, Amit Ron, Khanh-Hoa Tran-Ba, Rhodora C Calizo, Iman Tavassoly, Smiti Bhattacharya, Gomathi Jayaraman, Yibang Chen, Vera Rabinovich, Ravi Iyengar, James C Hone, John C He, Laura J Kaufman
Using a gelatin microbial transglutaminase (gelatin-mTG) cell culture platform tuned to exhibit stiffness spanning that of healthy and diseased glomeruli, we demonstrate that kidney podocytes show marked stiffness sensitivity. Podocyte-specific markers that are critical in the formation of the renal filtration barrier are found to be regulated in association with stiffness-mediated cellular behaviors. While podocytes typically de-differentiate in culture and show diminished physiological function in nephropathies characterized by altered tissue stiffness, we show that gelatin-mTG substrates with Young's modulus near that of healthy glomeruli elicit a pro-differentiation and maturation response in podocytes better than substrates either softer or stiffer...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28252641/mechanical-compression-induces-vegfa-overexpression-in-breast-cancer-via-dnmt3a-dependent-mir-9-downregulation
#14
Baek Gil Kim, Ming-Qing Gao, Suki Kang, Yoon Pyo Choi, Joo Hyun Lee, Ji Eun Kim, Hyun Ho Han, Seong Gyeong Mun, Nam Hoon Cho
Tumor growth generates mechanical compression, which may trigger mechanotransduction in cancer and stromal cells and promote tumor progression. However, very little is known about how compression stimulates signal transduction and contributes to tumor progression. In the present study, we demonstrated that compression enhances a tumor progression phenotype using an in vitro compression model, and validated the results from the in vitro model with high- and low-compressed breast cancer tissues. Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation in the MDA-MB-231 and BT-474 breast cancer cell lines and in cancer-associated fibroblasts...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28231640/mind-the-gap-mechanisms-regulating-the-endothelial-barrier
#15
REVIEW
Mariya Y Radeva, Jens Waschke
The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sieve-like manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue...
February 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28230212/establishment-of-planar-cell-polarity-is-coupled-to-regional-cell-cycle-exit-and-cell-differentiation-in-the-mouse-utricle
#16
Xiaoyu Yang, Xiaoqing Qian, Rui Ma, Xinwei Wang, Juanmei Yang, Wenwei Luo, Ping Chen, Fanglu Chi, Dongdong Ren
Sensory hair cells are coordinately oriented within each inner ear sensory organ to exhibit a particular form of planar cell polarity (PCP) necessary for mechanotransduction. However, the developmental events associated with establishing PCP in the vestibule are unclear, hindering data interpretation and employment of the vestibule for PCP studies. Herein, we investigated PCP of the mouse vestibular organs. We further characterised cell cycle exit, cell differentiation, and PCP establishment in the utricle...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220498/the-role-of-apical-cell-cell-junctions-and-associated-cytoskeleton-in-mechanotransduction
#17
REVIEW
Sophie Sluysmans, Ekaterina Vasileva, Domenica Spadaro, Jimit Shah, Florian Rouaud, Sandra Citi
Tissues of multicellular organisms are characterized by several types of specialized cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signaling. The machineries which functionally connect tight and adherens junctions to the cytoskeleton comprise proteins which either bind directly to cytoskeletal filaments, or function as adaptors for regulators of the assembly and function of the cytoskeleton...
February 21, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28219986/functional-analysis-of-the-transmembrane-and-cytoplasmic-domains-of-pcdh15a-in-zebrafish-hair-cells
#18
Reo Maeda, Itallia V Pacentine, Timothy Erickson, Teresa Nicolson
Protocadherin 15 (PCDH15) is required for mechanotransduction in sensory hair cells as a component of the tip link. Isoforms of PCDH15 differ in their cytoplasmic domains (CD1, CD2, and CD3), but share the extracellular and transmembrane (TMD) domains, as well as an intracellular domain known as the common region (CR). In heterologous expression systems, both the TMD and CR of PCDH15 have been shown to interact with members of the mechanotransduction complex. The in vivo significance of these protein-protein interaction domains of PCDH15 in hair cells has not been determined...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28211170/endothelial-glycocalyx-as-a-critical-signalling-platform-integrating-the-extracellular-haemodynamic-forces-and-chemical-signalling
#19
REVIEW
Ye Zeng
The glycocalyx covers the human mammalian cells and plays important roles in stroke, inflammation and atherosclerosis. It has also been shown to be involved in endothelial mechanotransduction of shear stress. Shear stress induces the remodelling of the major component of the glycocalyx including glypican-1, a cell membrane heparan sulphate proteoglycan. Other factors, such as sphingosine-1-phosphate (S1P), protect the glycocalyx against syndecan-1 ectodomain shedding and induce the synthesis of heparan sulphate...
February 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28209736/pejvakin-a-candidate-stereociliary-rootlet-protein-regulates-hair-cell-function-in-a-cell-autonomous-manner
#20
Marcin Kazmierczak, Piotr Kazmierczak, Anthony W Peng, Suzan L Harris, Prahar Shah, Jean-Luc Puel, Marc Lenoir, Santos J Franco, Martin Schwander
Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and co-localizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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