Publication: Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3:
Putative molecular components of the oxygen and
glucose sensing apparatus in articular chondrocytes
Authors
Mobasheri, A. ; Richardson, S. ; Mobasheri, R. ; Shakibaei, M. ; Hoyland, J.A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Articular cartilage is an avascular connective
tissue in which the availability of oxygen and glucose is
significantly lower than synovial fluid and plasma.
Glucose is an important metabolic fuel and structural
precursor that plays a key role in the synthesis of
extracellular matrix macromolecules in articular
cartilage. However, glucose concentrations in cartilage
can fluctuate depending on age, physical activity and
endocrine status. Chondrocytes are glycolytic cells and
must be able to sense the quantities of oxygen and
glucose available to them in the extracellular matrix and
respond appropriately by adjusting cellular metabolism.
Consequently chondrocytes must have the capacity to
survive in an extracellular matrix with limited nutrients
and low oxygen tensions. The molecular mechanisms
responsible for allowing chondrocytes to adapt to these
harsh environmental conditions are poorly understood.
In this article we present a novel “dual” model of oxygen
and glucose sensing in chondrocytes based on recent
experimental data. This model incorporates the hypoxiainducible
factor alpha (HIF-1a) as an oxygen sensor and
the hypoxia responsive facilitative glucose transporters,
GLUT1 and GLUT3 as putative components of the
glucose sensing apparatus in chondrocytes. Recent
studies have shown that GLUT1 and GLUT3 are both
expressed in chondrocytes and their HIF-1a-mediated transcription may be dually stimulated in response to
hypoxia and low glucose conditions which in turn
promote anaerobic glycolysis in favor of oxidative
phosphorylation. This working model provides, for the first time, a unifying hypothesis to explain how
chondrocytes might sense and respond to low oxygen
tensions and alterations in extracellular glucose.
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