Differentiation-induced loss of heparan sulfate in human exostosis derived chondrocytes
Abstract 2005 MHE Conference
Jacqueline T. Hecht 1,2 Richard Haynes 2, William G. Cole 3,
Robert J. Long 4, Mary C. Farach-Carson 4, Daniel D. Carson 4
1 University of Texas Medical School at Houston,
2 Shriners Hospital-Houston, Houston,
3 Department of Surgery, Hospital for Sick Children, Toronto, Canada,
4 Department of Biological Sciences, University of Delaware
An exostosis or osteochondroma is an aberrant bony growth occurring next to the growth plate
either as an isolated growth abnormality or as part of the Hereditary Multiple Exostosis (HME)
syndrome.
Mutations in either exostosin 1 (EXT1) or exostosin 2 (EXT2) gene cause the HME syndrome and
also some isolated osteochondromas.
The EXT1 and EXT2 genes are glycosyltransferases that function as hetero-oligomers in the Golgi to
add repeating glycosaminoglycans (GAGs) to heparan sulfate (HS) chains. Previously, we
demonstrated that HS is markedly diminished in the exostosis cartilage cap and that the HS
proteoglycan, perlecan, has an abnormal distribution in these caps.
The present studies were undertaken to evaluate which chondrocyte-specific functions are
associated with diminished HS synthesis in human chondrocytes harboring either EXT1 or EXT2
mutations.
Systematic evaluation of exostosis cartilage caps and chondrocytes, both in vitro and in vivo,
suggests that chondrocyte-specific cell functions account for diminished HS levels. In addition, we
provide evidence that perichondrial cells give rise to chondrocytes that clonally expand and develop
into an exostosis.
Undifferentiated EXT chondrocytes synthesized amounts of HS similar to control chondrocytes;
however, EXT chondrocytes displayed very poor survival in vitro under conditions that promote
normal chondrocyte differentiation with high efficiency.
Collectively, these observations suggest that loss of one copy of either the EXT1 or EXT2 gene
product compromises the perichondrial chondrocytes’ ability to differentiate normally and to survive
in a differentiated state in vitro. In vivo, these compromised responses may lead to abnormal
chondrocyte growth, perhaps from a perichondrial stem cell reserve.
Abstract 2005 MHE Conference
Jacqueline T. Hecht 1,2 Richard Haynes 2, William G. Cole 3,
Robert J. Long 4, Mary C. Farach-Carson 4, Daniel D. Carson 4
1 University of Texas Medical School at Houston,
2 Shriners Hospital-Houston, Houston,
3 Department of Surgery, Hospital for Sick Children, Toronto, Canada,
4 Department of Biological Sciences, University of Delaware
An exostosis or osteochondroma is an aberrant bony growth occurring next to the growth plate
either as an isolated growth abnormality or as part of the Hereditary Multiple Exostosis (HME)
syndrome.
Mutations in either exostosin 1 (EXT1) or exostosin 2 (EXT2) gene cause the HME syndrome and
also some isolated osteochondromas.
The EXT1 and EXT2 genes are glycosyltransferases that function as hetero-oligomers in the Golgi to
add repeating glycosaminoglycans (GAGs) to heparan sulfate (HS) chains. Previously, we
demonstrated that HS is markedly diminished in the exostosis cartilage cap and that the HS
proteoglycan, perlecan, has an abnormal distribution in these caps.
The present studies were undertaken to evaluate which chondrocyte-specific functions are
associated with diminished HS synthesis in human chondrocytes harboring either EXT1 or EXT2
mutations.
Systematic evaluation of exostosis cartilage caps and chondrocytes, both in vitro and in vivo,
suggests that chondrocyte-specific cell functions account for diminished HS levels. In addition, we
provide evidence that perichondrial cells give rise to chondrocytes that clonally expand and develop
into an exostosis.
Undifferentiated EXT chondrocytes synthesized amounts of HS similar to control chondrocytes;
however, EXT chondrocytes displayed very poor survival in vitro under conditions that promote
normal chondrocyte differentiation with high efficiency.
Collectively, these observations suggest that loss of one copy of either the EXT1 or EXT2 gene
product compromises the perichondrial chondrocytes’ ability to differentiate normally and to survive
in a differentiated state in vitro. In vivo, these compromised responses may lead to abnormal
chondrocyte growth, perhaps from a perichondrial stem cell reserve.
Research authored by Dr. Hecht
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
Jacqueline Hecht, PH.D.
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National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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