Previously, we have performed subtractive hybridization to identify genes up-regulated in hypertrophic chondrocytes of the avian epiphyseal growth plate. In the present study, we report the identification of one of the clones as UDP-glucose pyrophosphorylase (UDPG-PPase) and propose a possible function for this enzyme in regulating hyaluronan (HA) synthesis in hypertrophic cartilage. We have cloned the 2.6kb full-length cDNA for avian UDPG-PPase and confirmed its up-regulation in hypertrophic versus non-hypertrophic cartilage by Northern-blot analysis. The 6-fold increase in mRNA was paralleled by an equivalent increase in enzymic activity. The enzyme catalyses the conversion of glucose 1-phosphate into UDP-glucose, which is used to synthesize a number of cellular components, including HA. Overexpression of enzymically active UDPG-PPase in non-hypertrophic chondrocytes resulted in a 2–3-fold increase in total HA, as determined by a competitive binding assay and immunohistochemistry. In the developing growth plate, HA synthesis was elevated in the hypertrophic zone along with the up-regulation of the HA synthase (HAS)-2 gene. Our data suggest that an increase in both activities, UDPG-PPase and HAS-2, is required for non-hypertrophic chondrocytes to synthesize an amount of HA comparable with that in hypertrophic chondrocytes. Therefore we conclude that HA synthesis during chondrocyte differentiation is regulated at the level of the substrate-provider gene, UDPG-PPase, as well as the HAS genes.
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December 2001
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Research Article|
December 10 2001
UDP-glucose pyrophosphorylase: up-regulation in hypertrophic cartilage and role in hyaluronan synthesis
Cordula MAGEE;
Cordula MAGEE
Department of Anatomy and Cellular Biology, Tufts University Medical School, 136 Harrison Avenue, Boston, MA 02111, U.S.A.
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Maria NURMINSKAYA;
Maria NURMINSKAYA
Department of Anatomy and Cellular Biology, Tufts University Medical School, 136 Harrison Avenue, Boston, MA 02111, U.S.A.
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Thomas F. LINSENMAYER
Thomas F. LINSENMAYER
1
Department of Anatomy and Cellular Biology, Tufts University Medical School, 136 Harrison Avenue, Boston, MA 02111, U.S.A.
1To whom correspondence should be addressed (e-mail thomas.linsenmayer@tufts.edu).
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Publisher: Portland Press Ltd
Received:
June 25 2001
Revision Received:
September 07 2001
Accepted:
October 18 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 360 (3): 667–674.
Article history
Received:
June 25 2001
Revision Received:
September 07 2001
Accepted:
October 18 2001
Citation
Cordula MAGEE, Maria NURMINSKAYA, Thomas F. LINSENMAYER; UDP-glucose pyrophosphorylase: up-regulation in hypertrophic cartilage and role in hyaluronan synthesis. Biochem J 15 December 2001; 360 (3): 667–674. doi: https://doi.org/10.1042/bj3600667
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