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Potential therapeutic effects of galectin-9 in osteoarthritis (EPSRC).

Principal investigator: C. Cervone
Co-investigator(s): D. Cooper, M. Peretti, N. Peake, and Tina CHOWDHURY

There is an urgent demand for long-term solutions to improve osteoarthritis (OA) treatment in the ageing population. There are drugs that control pain but none that halt the progression of the disease. Increased intervention efforts, augmented by early diagnosis and integrated physical therapies are therefore needed. IMF shows strong abundance of Gal-3 (green; F) and Gal-9 expression (green; H) in human OA cartilage when compared to normal tissue (E, G). Co-localisation with lubricin (I, K) or CD44 (J, L) shows greater abundance of Gal-3 in superficial and deep zone cartilage. Gal-9 was strongly expressed by deep zone cells from older tissue (red, L). This project will utilise a cross-disciplinary approach to determine the potential therapeutic effect of galectins in a human chondrocyte 3D/bioreactor model. Galectins (Gal-1, 3 and 9) are emerging as key regulators in several pathophysiological processes including cell adhesion, apoptosis, inflammatory and autoimmune responses. However, few studies have addressed the role of galectins in cartilage biology and OA. Several lines of evidence implicate a role for the galectins in chondrocytes including:

1) Gal-1 is detected intracellularly and in the extracellular environment of chondrocytes in vitro; exogenous Gal-1 downregulates anabolic gene expression.

2) Gal-3 is expressed by hypertrophic chondrocytes during bone development and relocalises to the cell surface in human OA chondrocytes.

3) Gal-9 administration induced cartilage repair in arthritic rats.

4) Endogenous Gal-9 induced differentiation of mesenchymal stem cells into chondrocytes and augments anabolic gene expression in the presence of TGFβ.

This EPSRC funded project involves collaboration with members at the WHRI (Dr Dianne Cooper, Prof Mauro Perretti) and will support a new PhD student due to start in Sept 2014.

Applications for PhD studentship starting Sept 2014: