Professor Timothy E Hardingham

Deputy Director UKCTE

Professor Tim Hardingham

Deputy Director, UK Centre for Tissue Engineering,

University of Manchester

Faculty of Life Sciences

Michael Smith Building

Oxford Road

MANCHESTER  M13 9PT

Tel:     +44 (0) 161 275 5511

Fax:    +44 (0) 161 275 5752

email:  timothy.e.hardingham@manchester.ac.uk

http://  www.wtccmr.man.ac.uk

http://www.ls.manchester.ac.uk/people/profile/index.asp?id=507

Proteoglycan Functions in the Extracellular Matrix

The formation, turnover repair of the extracellular matrix (ECM) are essential determinants of the growth and development of tissues into organs and of their healthy function in the body. Proteoglycans are specialised proteins with long polyanionic glycosaminoglycan chains attached and they are important molecular organisers of the ECM. Aggrecan is the major proteoglycan produced by chondrocytes in cartilage and we are using biochemical, molecular biology and biophysical techniques to investigate its functions. Gene constructs encoding normal and alternatively spliced aggrecan G3 domain have been expressed and we are determining their ligand binding properties and matrix function. A new approach using fluorescence recovery after photobleaching with a confocal microscope (confocal-FRAP) has been developed to measure molecular diffusion and thereby study interactions of ECM components. With this technique the networks formed by hyaluronan and aggrecan in solution and their permeability to FITC-labelled probes are being investigated at high concentrations close to those found within the ECM. This approach is also being applied to sections of cartilage to follow permeability changes that accompany matrix damage. We are also investigating the changes in gene expression in chondrocytes that accompany cartilage degeneration in osteoarthritis and the mechanisms of cartilage assembly by chondrocytes that are outlined in the accompanying UKCTE programme.