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Possible role of methylglyoxal and glyoxalase in arthritis

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Ahmed, Usman, Thornalley, Paul J. and Rabbani, Naila (2014) Possible role of methylglyoxal and glyoxalase in arthritis. Biochemical Society Transactions, Volume 42 (Number 2). pp. 538-542. doi:10.1042/BST20140024

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Official URL: http://dx.doi.org/10.1042/BST20140024

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Abstract

OA (osteoarthritis) and RA (rheumatoid arthritis) lead to deterioration of the joints. Early OA is associated with loss of bone due to increased bone remodelling. A role for inflammation is thought to be integral to the pathology. RA is a chronic inflammatory disease of the synovium, a membrane lining the non-weight-bearing surfaces of the joint. The mainstay of RA diagnostic testing is for autoantibodies. Rheumatoid factor has been a primary diagnostic test; however, sensitivity is approximately 75%, but specificity is limited. Recently, detection of antibodies against cyclic citrullinated peptide, identified as a screening marker and marker of disease progression, has been proposed. Studies of glycation in arthritis have focused mostly on levels of AGEs (advanced glycation end-products), Nε-carboxymethyl-lysine and pentosidine. There was a weak correlation of skin and urinary pentosidine with joint damage in early-stage OA. RAGE (receptor for AGEs) is a cell-surface receptor in the synovial tissue of patients with OA and RA. The RAGE agonist S100A12 is increased in RA and OA. Activation of RAGE may decrease expression of Glo1 (glyoxalase I). Conflict between RAGE-activated inflammatory signalling and Nrf2 (nuclear factor-erythroid 2-related factor 2) regulation of basal and inducible expression of Glo1 may be involved. Thereby glyoxal- and methylglyoxal-derived AGEs may be increased in OA and RA. Further studies are now required to investigate the role of glyoxalase and dicarbonyl glycation in OA and RA for early-stage diagnosis and potential novel preventive therapy.

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Biochemical Society Transactions
Publisher: Portland Press Ltd
ISSN: 0300-5127
Official Date: April 2014
Dates:
DateEvent
April 2014Published
14 January 2014Submitted
Volume: Volume 42
Number: Number 2
Page Range: pp. 538-542
DOI: 10.1042/BST20140024
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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