Functional characterisation of glucose transport in bovine articular chondrocytes.
The adequate provision of glucose to articular chondrocytes is essential to sustain their predominantly anaerobic metabolism; glucose is also a precursor for the extracellular matrix macromolecules which these cells synthesise. Impaired glucose uptake would compromise cell function and potentially result in an imbalance of matrix synthesis and degradation, leading to osteoarthritis. We studied the glucose influx pathway into bovine articular chondrocytes using 2-deoxy- d-[(3)H]-glucose (DOG). Uptake occurs via an extracellular pH (pH(o))-insensitive, phloretin- and cytochalasin B-sensitive pathway, hallmarks of the GLUT family of facilitative glucose transporters, with a K(m) of 0.35+/-0.11 mM. Uptake was affected by a number of physiologically relevant factors: (1) raised hydrostatic pressure (1-30 MPa) inhibited DOG uptake by up to 30%; (2) interleukin-1 (IL-1beta) reduced uptake via an increase in transporter affinity; (3) glucosamine inhibited glucose uptake in a manner consistent with the actions of a competitive inhibitor. Given the involvement of IL-1beta in osteoarthritis and the protective role assigned to glucosamine, these findings implicate an important role for glucose delivery in chondrocyte energy production and matrix metabolism, which, therefore, may potentially affect the maintenance of cartilage integrity.
Windhaber
Robin A J
RA
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
Wilkins
Robert J
RJ
Meredith
David
D
D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism*; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D013696:Temperature
D000963:Antimetabolites; D007375:Interleukin-1; D003847:Deoxyglucose; D005947:Glucose; D005944:Glucosamine