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Title: Expression and function of NG2/HMPG in human cartilage
Author: Midwood, Kim Suzanne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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In view of the expression of NG2 by developing cartilage in rats and putative roles in cell-matrix interactions we have investigated the expression of NG2 by normal human cartilage and adult osteoarthritic cartilage and its potential to function as a cell signalling molecule. Cryostat sections of human fetal knee joints and articular cartilage from macroscopically normal and osteoarthritic adult knee joints obtained at autopsy were immunostained with a panel of antibodies against rat NG2 and HMPG. Chondrocytes in fetal cartilage and normal adult cartilage showed strong immunoreactivity with anti-NG2/HMPG antibodies. NG2 is also present in osteoarthritic cartilage, but expression is down regulated. Western blots of whole cell lysates from macroscopically normal and OA femoral chondyles, revealed a smeared component of molecular weight greater than 400 kD and a faint band at 250 kD. The 250 kD protein became predominant upon digestion with chondroitinase ABC. Autoradiographs of I125 labelled chondrocyte lysates which had been precipitated with anti-HMPG antibody confirmed NG2 was present in human adult articular chondrocytes. Immunofluorescence staining of cultured chondrocytes revealed that NG2 is distributed in a punctate pericellular pattern. These studies show that NG2 is expressed by human fetal and adult chondrocytes. In adult articular chondrocytes the core protein is chondroitin sulphated and both CS modified and CS free forms are simultaneously expressed. Expression is down regulated in OA cells. NG2 appears to influence chondrocyte interaction with type VI collagen, via a pertussis sensitive G protein. Cell matrix binding functions and cell signalling activity suggest that NG2/HMPG has important roles in the regulation of articular chondrocyte activity in health and disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available