scholarly journals The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 972 ◽  
Author(s):  
Heinrich Kovar ◽  
Lisa Bierbaumer ◽  
Branka Radic-Sarikas
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Bone Tumors ◽  
Developmental Stages ◽  
Current Knowledge ◽  
Bone Development ◽  
Matrix Composition ◽  
Distinct Cell Type ◽  
Extracellular Matrix Components ◽  
Differentiation Stage

YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.

scholarly journals A Strategy to Enhance Secretion of Extracellular Matrix Components by Stem Cells: Relevance to Tissue Engineering

2018 ◽  
Vol 24 (1-2) ◽  
pp. 145-156 ◽  
Author(s):  
Navaneethakrishnan Krishnamoorthy ◽  
Yuan‐Tsan Tseng ◽  
Poornima Gajendrarao ◽  
Padmini Sarathchandra ◽  
Ann McCormack ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Extracellular Matrix ◽  
Extracellular Matrix Components ◽  
Matrix Components

scholarly journals Influence of obesity on remodeling of lung tissue and organization of extracellular matrix after blunt thorax trauma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pengfei Xu ◽  
Fabian Gärtner ◽  
Adrian Gihring ◽  
Congxing Liu ◽  
Timo Burster ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Tissue ◽  
Protein Level ◽  
Morphological Changes ◽  
Matrix Composition ◽  
Collagen Deposition ◽  
Obese Mice ◽  
Time Points ◽  
Extracellular Matrix Components ◽  
Thorax Trauma

Abstract Background Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet. Methods This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h). Results Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%. Conclusions In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.

scholarly journals The Role of Extracellular Matrix Components in Dentin Mineralization

1991 ◽  
Vol 2 (3) ◽  
pp. 369-387 ◽  
Author(s):  
Adele L. Boskey
Keyword(s):  
Extracellular Matrix ◽  
Current Knowledge ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Crystal Formation ◽  
Extracellular Matrix Components ◽  
Dentin Mineralization ◽  
Matrix Maturation ◽  
Cell Matrix Interactions

The extracellular matrix of dentin consists of mineral (hydroxyapatite), collagen, and several noncollagenous matrix proteins. These noncollagenous matrix proteins may be mediators of cell-matrix interactions, matrix maturation, and mineralization. This review describes the current knowledge of the chemistry of mineral crystal formation in dentin with special emphasis on the roles of the dentin matrix proteins. The functions of some of these matrix proteins in the mineralization process have been deduced based on in vitro studies. Functions for others have been postulated based on analogy with some of the bone matrix proteins. Evidence suggests that several of these matrix proteins may have multiple effects on nucleation, crystal growth, and orientation of dentin hydroxyapatite.

scholarly journals Presence of ROS in Inflammatory Environment of Peri-Implantitis Tissue: In Vitro and In Vivo Human Evidence

2019 ◽  
Vol 9 (1) ◽  
pp. 38
Author(s):  
Eitan Mijiritsky ◽  
Letizia Ferroni ◽  
Chiara Gardin ◽  
Oren Peleg ◽  
Alper Gultekin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Human Model ◽  
Inflammatory Cell Infiltrate ◽  
Mitochondrial Activity ◽  
Type I ◽  
Biological Organization ◽  
Extracellular Matrix Components ◽  
Matrix Components

Analyses of composition, distribution of cellular and extracellular matrix components, and molecular analysis of mitochondria related genes of bone loss in the presence of inflammatory environment in humans was the aim of the present project. As a human model we chose peri-implantitis. Morphological analyses were performed by means classical histological, immunohistochemical, and SEM (scanning electron miscroscopy) test. Gene expression analysis was performed to evaluate epithelium maturation, collagen fiber production, and genes related to mitochondrial activity. It was found that a well-defined keratinocyte epithelium was present on the top of all specimens; a distinct basal lamina was present, as well as desmosomes and autophagic processes related to the maturation of keratinocytes. Under this epithelium, a full inflammatory cell infiltrate was present for about 60% of the represented by plasma cells. Collagen type I fibers were present mainly in the form of fragmented cord tissue without cells. A different distribution of blood vessels was also present from the apical to the most coronal portion of the specimens. High levels of genes related to oxidative stress were present, as well as the activation of genes related to the loss of ability of osteogenic commitment of Mesenchymal stem cells into osteoblasts. Our study suggests that peri-implantitis lesions exhibit a well defined biological organization not only in terms of inflammatory cells but also on vessel and extracellular matrix components even if no difference in the epithelium is evident, and that the presence of reactive oxygen species (ROS) related to the inflammatory environment influences the correct commitment of Mesenchymal stem cells.

scholarly journals Extracellular matrix modulates the biological effects of melatonin in mesenchymal stem cells

2014 ◽  
Vol 223 (2) ◽  
pp. 167-180 ◽  
Author(s):  
Fan He ◽  
Xiaozhen Liu ◽  
Ke Xiong ◽  
Sijin Chen ◽  
Long Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Biological Effects ◽  
Matrix Composition ◽  
Calcium Deposition ◽  
Specific Gene ◽  
Skeletal Tissue ◽  
Underlying Mechanisms

Both self-renewal and lineage-specific differentiation of mesenchymal stem cells (MSCs) are triggered by theirin vivomicroenvironment including the extracellular matrix (ECM) and secreted hormones. The ECM may modulate the physiological functions of hormones by providing binding sites and by regulating downstream signaling pathways. Thus, the purpose of this study was to evaluate the degree of adsorption of melatonin to a natural cell-deposited ECM and the effects of this interaction on the biological functions of melatonin in human bone marrow-derived MSCs (BM-MSCs). The fibrillar microstructure, matrix composition, and melatonin-binding affinity of decellularized ECM were characterized. The cell-deposited ECM improved melatonin-mediated cell proliferation by 31.4%, attenuated accumulation of intracellular reactive oxygen species accumulation, and increased superoxide dismutase (SOD) mRNA and protein expression. Interaction with ECM significantly enhanced the osteogenic effects of melatonin on BM-MSCs by increasing calcium deposition by 30.5%, up-regulating osteoblast-specific gene expression and down-regulating matrix metalloproteinase (MMP) expression. The underlying mechanisms of these changes in expression may involve intracellular antioxidant enzymes, because osteoblast-specific genes were down-regulated, whereas MMP expression was up-regulated, in the presence of SOD-specific inhibitors. Collectively, our findings indicate the importance of native ECM in modulating the osteoinductive and antioxidant effects of melatonin and provide a novel platform for studying the biological actions of growth factors or hormones in a physiologically relevant microenvironment. Moreover, a better understanding of the enhancement of MSC growth and osteogenic differentiation resulting from the combination of ECM and melatonin could improve the design of graft substitutes for skeletal tissue engineering.

scholarly journals Endothelial cell polarity and extracellular matrix production rely on functional ATP6AP2 during developmental and pathological angiogenesis

2021 ◽  
Author(s):  
NR Patel ◽  
A Blanks ◽  
Y Li ◽  
MC Prieto ◽  
SM Meadows
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Polarity ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Matrix Composition ◽  
Pathological Angiogenesis ◽  
Extracellular Matrix Components

AbstractThe (Pro)renin receptor ((P)RR), also known as ATP6AP2, is a single-transmembrane protein that is implicated in a multitude of biological processes. However, the exact role of ATP6AP2 during blood vessel development remains largely undefined. Here, we use an inducible endothelial cell (EC)-specific Atp6ap2 knockout mouse model to investigate the role of ATP6AP2 during both physiological and pathological angiogenesis in vivo. We observed that postnatal deletion of Atp6ap2 in ECs results in cell migration defects, loss of tip cell polarity and subsequent impairment of retinal angiogenesis. In vitro, Atp6ap2 deficient ECs similarly displayed reduced cell migration, impaired sprouting, and defective cell polarity. Transcriptional profiling of ECs isolated from Atp6ap2 mutant mice further indicated regulatory roles in angiogenesis, cell migration and extracellular matrix composition. Mechanistically, we showed that expression of various extracellular matrix components is controlled by ATP6AP2 via the extracellular-signal-regulated kinase (ERK) pathway. Furthermore, Atp6ap2 deficient retinas exhibited reduced revascularization in an oxygen induced retinopathy model. Collectively, our results demonstrated a critical role of ATP6AP2 as a regulator of developmental and pathological angiogenesis.

scholarly journals Can We Build Artificial Stem Cell Compartments?

2003 ◽  
Vol 2003 (3) ◽  
pp. 164-169 ◽  
Author(s):  
Carlos E. Semino
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Three Dimensional ◽  
Soluble Factors ◽  
Cell Compartments ◽  
Synthetic Materials ◽  
Extracellular Matrix Components ◽  
Main Factors ◽  
Matrix Components

Animals carry stem cells throughout their entire life, from embryogenesis to senescence. Their function during development and adulthood consists basically of forming and sustaining functional tissues while maintaining a small self-renewing population. They reside in a complex three-dimensional environment consisting of other nearby cells extracellular matrix components, endogenous or exogenous soluble factors, and physical, structural, or mechanical properties of the tissues they inhabit. Can we artificially recreate tissue development such that stem cells can both self-renew and be instructed to mature properly? The main factors required to regulate the maintenance and differentiation of some types of stem cells are known. In addition, new bioengineered synthetic materials that mimic extracellular matrix components can be used as initial scaffolding for building stem cell microenvironments.

scholarly journals Thyroid Cancer Stem-Like Cells: From Microenvironmental Niches to Therapeutic Strategies

2021 ◽  
Vol 10 (7) ◽  
pp. 1455
Author(s):  
Elisa Stellaria Grassi ◽  
Viola Ghiandai ◽  
Luca Persani
Keyword(s):  
Extracellular Matrix ◽  
Thyroid Cancer ◽  
Cancer Biology ◽  
Recent Progress ◽  
Current Knowledge ◽  
Metastatic Potential ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Matrix Composition ◽  
Stem Cell Niches

Thyroid cancer (TC) is the most common endocrine malignancy. Recent progress in thyroid cancer biology revealed a certain degree of intratumoral heterogeneity, highlighting the coexistence of cellular subpopulations with distinct proliferative capacities and differentiation abilities. Among those subpopulations, cancer stem-like cells (CSCs) are hypothesized to drive TC heterogeneity, contributing to its metastatic potential and therapy resistance. CSCs principally exist in tumor areas with specific microenvironmental conditions, the so-called stem cell niches. In particular, in thyroid cancer, CSCs’ survival is enhanced in the hypoxic niche, the immune niche, and some areas with specific extracellular matrix composition. In this review, we summarize the current knowledge about thyroid CSCs, the tumoral niches that allow their survival, and the implications for TC therapy.

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