Molecular
characterization and partial cDNA cloning of facilitative glucose transporters
expressed in human articular chondrocytes; stimulation of 2-deoxyglucose uptake
by IGF-I and elevated MMP-2 secretion by glucose deprivation
subject: articular
chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and elevated MMP-2
secretion
object_opposite: glucose deprivation/chondrocyte
diminution
misc: Osteoarthritis and Cartilage
Volume 11, Issue 2, February 2003, Pages 92–10 Molecular characterization and
partial cDNA cloning of facilitative glucose transporters expressed in human
articular chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and
elevated MMP-2 secretion by glucose deprivation
author_year: S Richardsona/G Neamaa/T
Phillipsa/S Bella/S.D Cartera/K.H Moleyb/J.F Moleyc/S.J Vannuccid/A
Mobasheria/2003
journal_volume_page: Osteoarthritis and Cartilage
Volume 11/Issue 2/ Pages 92–10
Abstract
Objective Recent
evidence suggests that human chondrocytes express several facilitative glucose
transporter (GLUT) isoforms and also that 2-deoxyglucose transport is
accelerated by cytokine stimulation. The aim of the present investigation was
to determine if human articular chondrocytes express any of the recently
identified members of the GLUT/SLC2A gene family and to examine the effects of
endocrine factors, such as insulin and IGF-I on the capacity of human
chondrocytes for transporting 2-deoxyglucose.
Design/methods PCR,
cloning and immunohistochemistry were employed to study the expression of
GLUT/SLC2A transporters in normal human articular cartilage. The uptake of
2-deoxyglucose was examined in monolayer cultured immortalized human
chondrocytes following stimulation with TNF-α, insulin and IGF-I. Levels of
MMP-2 were assessed by gelatin zymography following glucose deprivation of
alginate cultures.
Results Using
PCR we detected transcripts for eight glucose transporter isoforms (GLUTs 1, 3,
6, 8, 9, 10, 11 and 12) and for a fructose transporter (GLUT5) in human
articular cartilage. Expression of GLUT1, GLUT3 and GLUT9 proteins in normal human
articular cartilage was confirmed by immunohistochemistry. The uptake of
2-deoxyglucose was dependent on time and temperature, inhibited by cytochalasin
B and phloretin, and significantly accelerated in chondrocyte cultures
stimulated with IGF-I. However, 2-deoxyglucose uptake was unaffected by short
and long-term insulin treatment, which ruled out a functional role for
insulin-sensitive GLUT4-mediated glucose transport. Furthermore, secretion of
MMP-2 was
subject: articular
chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and elevated MMP-2
secretion
object_opposite: glucose deprivation
misc: Osteoarthritis and Cartilage
Volume 11, Issue 2, February 2003, Pages 92–10 Molecular characterization and
partial cDNA cloning of facilitative glucose transporters expressed in human
articular chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and
elevated MMP-2 secretion by glucose deprivation
author_year: S Richardsona/G Neamaa/T
Phillipsa/S Bella/S.D Cartera/K.H Moleyb/J.F Moleyc/S.J Vannuccid/A
Mobasheria/2003
journal_volume_page: Osteoarthritis and Cartilage
Volume 11/Issue 2/ Pages 92–10increased in alginate
cultures deprived of glucose.
Conclusions The
data supports a critical role for glucose transport and metabolism in the
synthesis and degradation of cartilage. Copyright 2002 OsteoArthritis
Research Society International. Published by Elsevier Science Ltd. All rights
reserved.
Keywords
·
Chondrocyte, Cartilage, Glucose transport, GLUT, IGF-I, Insulin,
MMP-2.
