Mechanisms of joint damage in chronic gout: The role of stromal cells

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dc.contributor.advisor Dalbeth, N en
dc.contributor.advisor Cornish, J en
dc.contributor.advisor Naot, D en Chhana, Ashika en 2013-12-02T19:14:26Z en 2013 en
dc.identifier.uri en
dc.description.abstract Gout is an inflammatory arthritis caused by the deposition of monosodium urate (MSU) monohydrate crystals within and around the joint. It is the most common form of inflammatory arthritis affecting men and is a major cause of musculoskeletal disability in New Zealand. Cartilage and bone erosion are frequently observed in patients with chronic gout, and tendon rupture has also been observed in these patients. The mechanisms of joint damage in chronic gout are not yet fully understood. The aim of this work was to determine the role of stromal cells in the development of joint damage in chronic gout. Osteoblasts, chondrocytes and tenocytes isolated from primary tissues or appropriate cell lines were cultured in vitro with MSU crystals and changes in viability, gene expression, differentiation and function were analysed. The main findings of this study included reduced viability of all cell types tested; inhibition of mineralisation by osteoblasts and collagen deposition by chondrocytes and tenocytes; and decreased gene expression of osteoblastic, chondrocytic and tenocytic markers including collagens and cell-specific transcription factors and proteins. In addition, the gene expression levels of degradative aggrecanases were upregulated in chondrocytes cultured with MSU crystals. These in vitro findings were supported by analysis of joint samples from patients with chronic gout. In bone samples, osteoblast and lining cell numbers were reduced at sites adjacent to tophus, but not at sites away from tophus. Cartilage in these patients was highly disordered with a loss of normal architecture, and fragments of degenerative cartilage with few or no living chondrocytes were often observed. MSU crystals and tophaceous material were also identified invading tendon, within tendon and at the tendon-bone insertion site. These results suggest that stromal cells play an important role in the development and progression of joint damage in chronic gout, both through active degradation of joint tissues and reduced viability and function, which may limit the ability of the joint to repair itself following degradation. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.title Mechanisms of joint damage in chronic gout: The role of stromal cells en
dc.type Thesis en The University of Auckland en Doctoral en PhD en
dc.rights.holder Copyright: The Author en en
dc.rights.accessrights en
pubs.elements-id 413632 en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en
pubs.record-created-at-source-date 2013-12-03 en

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