RICERCA ITALIANA     

EXTRACELLULAR MATRIX: REGULATORY PHENOMENA, INTERMOLECULAR INTERACTIONS AND FUNCTIONAL MODIFICATIONS

Università degli Studi di Bologna

Abstract

The extracellular matrix (ECM) is a substance underlying all epithelia and endothelia and surrounding all the cells of connective tissues, thus giving tissues and organs mechanical support and physical resistance. In addition to its merely mechanical functions, the ECM strongly influences cell behaviour (adhesion, diffusion, migration) and the patterns of gene expression in adjacent cells.
The ECM comprises structural molecules such as fibrillar and non fibrillar collagens, proteoglycans (PGs) and, in elastic connective tissues, elastin fibers. Changes in the composition of these elements and their interactions give rise to different tissues with a different functional role and response.
The goal of this project is to analyze "in vitro" the interactions that small leucine- rich proteoglycans (SLRPs) have with fibrillar collagens and with syntetic peptides or obtained from specific fragmentation ( CNBr peptides); to analyze the behavior and the modifications received "in vivo" from ECM when it is found to be in functional conditions of particular clinical interest, such as muscle-tendon stretching; to analyze the interaction of titanium implants with host bone.
We expect to find modifications of the ECM under functional stimuli and therefore to evaluate the possible consequences at a physiological and functional level.
Unit 3 aims to examine the type of binding that SLRPs such as decorin (DCN), fibromodulin (FM) and biglycan (BGN) can contract >>>

Principal Investigator

Alessandro RUGGERI Università degli Studi di BOLOGNA

Research Objectives

Among many functions of the extracellular matrix (ECM) the role of physical support and resistance for tissues and organs has been widely studied by the project research units. In particular, we have focused on the structural and functional aspects of two ECM components: collagen fibrils and proteoglycans. Recent analysis of these components has moved to an in-depth study of their composition and reciprocal interactions under physiological conditions and to their possible adaptations when they are influenced by functional conditions different from the phisyological ones.
The project's objective is to investigate the limitations beyond which ECM components subjected to external stimuli undergo qualitative and quantitative changes and to analyze which of these components changes are compatible with ongoing physiological organization of the ECM.
The project will address possible changes in the constitution and structure of collagen fibrils in fibrous tissues (tendons) subjected to functional stimuli bordering on the limit of physiological conditions; the influence of metal surfaces of varying geometry and micromorphology on the osteogenic activity of bone tissue located at the interface; the influence of interactions of small proteoglycans belonging to fibrous tissues with fibrillar collagens when these collagens undergo treatments affecting their size or composition (using peptides from natural or synthetic sources) and chemical features (following >>>

First Results

By a study of the interactions between fibrillar collagens and SLRPs, we expect to characterize the relationship between analysed SLRPs (DCN, FM, BGN) and fibrillar collagens and their derivatives. The final purpose is to objectify and justify the variations of the interaction among these components in different metabolic and/or functional conditions.
By a morpho-functional study of the muscle-tendon unit subjected tostretching we expect to identify after a long-term treatment qualitative and quantitative variations of the ECM's components such as collagens and proteoglycans. In fact it is demonstrated that prolonged stretching leads to elongation of the muscle-tendon unit and it is likely that a qualitative as well as quantitative renewal of the components themselves would take place.
By a study of the relationship between bone matrix and implant surfaces with different roughness, we expect to find qualitative modifications of the ECM at the bone/implant interface.
These modifications may be detected "in vitro" by the analysis of matrix proteins selective adsorption and by the different behavior that osteoblasts, mesenchymal and endothelial cells may assume for their relationship with the surface.

Timescale

24 months

National and international background

The extracellular matrix (ECM) is a substance underlying any epithelium and endothelium and surrounding all connective tissue cells, thus giving tissues and organs mechanical support and physical resistance. In addition to its merely mechanical functions, the ECM strongly influences cell behaviour (adherence, diffusion, migration) and the patterns of gene expression in adjacent cells [1].
The ECM comprises structural molecules such as collagen fibrils, proteoglycans (PGs) and, in elastic connective tissues, elastin fibers. These constituents are associated with equally important glycoproteins and other protein molecules and form a three-dimensional network enveloping the cells and influencing their metabolic activity.
Changes in the composition of these elements and their interactions give rise to different tissues with a different functional role. Likewise, a complex system of cell to cell, cell to matrix and matrix to matrix interactions, as well as the production of enzymes, enzyme activators/inhibitors, growth factors, etc. underlies ECM remodelling.
Fibrillar collagens in particular (types I, II, III, V and XI) and proteoglycans are ubiquitous components and are present in all connective tissues. The structural and functional role of fibrillar collagens has been the subject of extensive research and the Laboratory of Electron Microscopy of the Institute of Human Anatomy in Bologna, in particular, has a long track of direct involvement in >>>