The Distribution of the Matricellular Protein Thrombospondin 2 in Tissues of Embryonic and Adult Mice

Mice that lack the matricellular protein thrombospondin 2 (TSP2) develop a pleiotropic phenotype characterized by morphological changes in connective tissues, an increase in vascular density, and a propensity for bleeding. Furthermore, dermal cells derived from TSP2-null mice display adhesion defects, a finding that implicates TSP2 in cell-matrix interactions. To gain a better understanding of the participation of TSP2 in the development and maturation of the mouse, we examined its distribution in embryonic and adult tissues. Special attention was paid to the presence of TSP2 in collagen fibers, because collagen fibrils in the TSP2-null mouse appear to be irregular in size and contour by electron microscopy. Immunohistochemical analysis of Day 15 and Day 18 embryos revealed TSP2 in areas of chondrogenesis, osteogenesis, and vasculogenesis, and in dermal and other connective tissue-forming cells. Distinctly different patterns of deposition of TSP2 were observed in areas of developing cartilage and bone at Days 15 and 18 of embryonic development. A survey of adult tissues revealed TSP2 in dermal fibroblasts, articular chondrocytes, Purkinje cells in the cerebellum, Leidig cells in the testis, and in the adrenal cortex. Dermal fibroblasts were also shown to synthesize TSP2 in vitro. The distribution of TSP2 during development is in keeping with its participation in the formation of a variety of connective tissues. In adult tissues, TSP2 is located in the pericellular environment, where it can potentially influence the cell-matrix interactions associated with cell movement and tissue repair.

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Cell-matrix interactions in cultured dermal fibroblasts from patients with an inherited connective-tissue disorder

Cytotechnology ◽

10.1007/bf00746072 ◽

1993 ◽

Vol 11 (S1) ◽

pp. S112-S114 ◽

Cited By ~ 5

Author(s):

M. Baccarani Contri ◽

R. Tiozzo ◽

M. A. Croce ◽

T. Andreoli ◽

A. De Paepe

Keyword(s):

Connective Tissue ◽

Connective Tissue Disorder ◽

Dermal Fibroblasts ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

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Origin and diversity of cardiac fibroblasts: developmental substrates of adult cardiac fibrosis

10.1093/med/9780198757269.003.0012 ◽

2018 ◽

Author(s):

Adrián Ruiz-Villalba ◽

Nikolaos Frangogiannis ◽

José Maria Pérez-Pomares

Keyword(s):

Cardiac Fibrosis ◽

Current Knowledge ◽

Cardiac Fibroblasts ◽

Experimental Models ◽

Common Element ◽

Connective Tissues ◽

Cardiac Morphogenesis ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

Cardiac connective tissues are primarily formed by cardiac fibroblasts (CF) of diverse embryonic origins. Whereas CF specific roles in cardiac morphogenesis remain under-researched, their involvement in adult cardiac fibrosis is clinically relevant. Cardiac fibrosis is a common element of several chronic cardiac conditions characterized by the loss of ventricular wall mechanical function, ultimately driving to heart failure. In the ischaemic heart early reparative fibrosis evidences the very restricted regenerative potential of the myocardium. In non-ischaemic diseases fibrosis is activated by unknown signals. We summarize current knowledge on the origin of CFs and their developmental roles, and discuss the differential disease-dependent response of different CF subpopulations to various pathological stimuli. We also describe the characteristic cell-cell and cell-matrix interactions that determine the fibrotic remodelling of the myocardium. We analyse experimental models for the study of cardiac fibrosis, and suggest future directions in the search for new markers and therapeutic targets.

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Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y99-055 ◽

1999 ◽

Vol 77 (7) ◽

pp. 465-480 ◽

Cited By ~ 84

Author(s):

Marie-Annick Forget ◽

Richard R Desrosiers ◽

Richard Béliveau

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinases ◽

Connective Tissues ◽

Cell Matrix ◽

Physiological Processes ◽

Matrix Interactions ◽

Tumor Growth And Metastasis ◽

Differentiation And Proliferation ◽

Cell Matrix Interactions ◽

Activation Cascade

Physiological processes involving remodelling of the extracellular matrix, such as wound healing, embryogenesis, angiogenesis, and the female reproductive cycle, require the activity of matrix metalloproteinases (MMPs). This group of proteases degrades basal membranes and connective tissues and plays an essential role in the homeostasis of the extracellular matrix. An imbalance in the expression or activity of MMPs can have important consequences in diseases such as multiple sclerosis, Alzheimer's disease, or the development of cancers. Because of the pathophysiological importance of MMPs, their activity is highly controlled in order to confine them to specific areas. An activation cascade, initiated by the proteolysis of plasminogen, cleaves proMMPs, and every step is controlled by specific activators or inhibitors. MMPs destabilize the organization of the extracellular matrix and influence the development of cancer by contributing to cell migration, tumor cell proliferation, and angiogenesis. Accordingly, these proteases possess an important role in cell-matrix interactions by affecting fundamental processes such as cell differentiation and proliferation. Therefore, the characterization of MMPs involved in specific types and stages of tumors will significantly improve the diagnosis and treatment of these cancers in humans.Key words: matrix metalloproteinases, physiology, cancer, cell invasion, extracellular matrix.

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Use of F9 teratocarcinoma STEM cells to study cell-matrix interactions in the early mouse embryo

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123416 ◽

1992 ◽

Vol 50 (1) ◽

pp. 602-603

Author(s):

Marc Lenburg ◽

Rulang Jiang ◽

Lengya Cheng ◽

Laura Grabel

Keyword(s):

Mouse Embryo ◽

Inner Cell Mass ◽

Cell Mass ◽

Cell Types ◽

Embryoid Bodies ◽

F9 Cells ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions ◽

F9 Teratocarcinoma

We are interested in defining the cell-cell and cell-matrix interactions that help direct the differentiation of extraembryonic endoderm in the peri-implantation mouse embryo. At the blastocyst stage the mouse embryo consists of an outer layer of trophectoderm surrounding the fluid-filled blastocoel cavity and an eccentrically located inner cell mass. On the free surface of the inner cell mass, facing the blastocoel cavity, a layer of primitive endoderm forms. Primitive endoderm then generates two distinct cell types; parietal endoderm (PE) which migrates along the inner surface of the trophectoderm and secretes large amounts of basement membrane components as well as tissue-type plasminogen activator (tPA), and visceral endoderm (VE), a columnar epithelial layer characterized by tight junctions, microvilli, and the synthesis and secretion of α-fetoprotein. As these events occur after implantation, we have turned to the F9 teratocarcinoma system as an in vitro model for examining the differentiation of these cell types. When F9 cells are treated in monolayer with retinoic acid plus cyclic-AMP, they differentiate into PE. In contrast, when F9 cells are treated in suspension with retinoic acid, they form embryoid bodies (EBs) which consist of an outer layer of VE and an inner core of undifferentiated stem cells. In addition, we have established that when VE containing embryoid bodies are plated on a fibronectin coated substrate, PE migrates onto the matrix and this interaction is inhibited by RGDS as well as antibodies directed against the β1 integrin subunit. This transition is accompanied by a significant increase in the level of tPA in the PE cells. Thus, the outgrowth system provides a spatially appropriate model for studying the differentiation and migration of PE from a VE precursor.

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Cell matrix interactions in asthma

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.1997.d01-423.x ◽

1997 ◽

Vol 27 (1) ◽

pp. 22-27

Author(s):

K. GOLDRING ◽

J. A. WARNER

Keyword(s):

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

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Cell-Matrix Interactions in Breast Carcinoma Invasion

10.21236/ada391446 ◽

2000 ◽

Author(s):

Anna M. Curatola

Keyword(s):

Breast Carcinoma ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

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A computational framework for modeling cell–matrix interactions in soft biological tissues

Biomechanics and Modeling in Mechanobiology ◽

10.1007/s10237-021-01480-2 ◽

2021 ◽

Author(s):

Jonas F. Eichinger ◽

Maximilian J. Grill ◽

Iman Davoodi Kermani ◽

Roland C. Aydin ◽

Wolfgang A. Wall ◽

...

Keyword(s):

Soft Tissues ◽

Three Dimensional ◽

Biological Tissues ◽

Computational Framework ◽

Cell Matrix ◽

Physiological Processes ◽

Matrix Interactions ◽

Mechanical Homeostasis ◽

Cell Matrix Interactions ◽

Short Time

AbstractLiving soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.

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