| Cytoskeletal Abnormalities in Hereditary Multiple Exostosis Chondrocytes |
Jacqueline T. Hecht, Ph.D.
Scientific Staff
Houston SHC
Professor, Department of Pediatrics
University of Texas Health Science Center Houston
The EXT genes are glycosyltransferases that synthesize heparan sulfate (HS) chains necessary for
the biological activity of HS proteoglycans that regulate growth plate proliferation and differentiation.
Mutations in the EXT1 and EXT2 genes cause Hereditary Multiple Exostoses (HME), an autosomal
dominant condition characterized by inappropriate bone growth at the ends of the long bones called
exostoses. Exostoses are numerous and often associated with orthopaedic complications requiring
multiple surgical interventions.
Scientific Staff
Houston SHC
Professor, Department of Pediatrics
University of Texas Health Science Center Houston
The EXT genes are glycosyltransferases that synthesize heparan sulfate (HS) chains necessary for
the biological activity of HS proteoglycans that regulate growth plate proliferation and differentiation.
Mutations in the EXT1 and EXT2 genes cause Hereditary Multiple Exostoses (HME), an autosomal
dominant condition characterized by inappropriate bone growth at the ends of the long bones called
exostoses. Exostoses are numerous and often associated with orthopaedic complications requiring
multiple surgical interventions.
Figure 2
Figure 2. Future studies will be aimed at gaining a better
understanding of normal mechanisms of bone growth which may
provide insights that will lead to nonsurgical intervention in HME.
understanding of normal mechanisms of bone growth which may
provide insights that will lead to nonsurgical intervention in HME.
Our studies have focused on exostosis chondrocytes to determine
how mutations affect the EXT protein levels and the chondrocyte
function.
Immunocytochemistry using EXT1 and EXT2 antibodies identified
significantly diminished levels of EXT1 and EXT2
proteins.Furthermore, exostosis chondrocytes have a unique
stellate appearance with elongated inclusions in the cytoplasm
composed of actin bundled by 1.5-mm repeat crossbridges of
a-actinin.
The exostosis chondrocytes produce aberrantly high levels of
muscle-specific a-actin, while b-actin levels are similar to normal
chondrocytes.
Altogether, these findings suggest that mutations in the EXT genes
affect the proteins regulating chondrocyte signaling. Our studies are
focused on identifying the proteoglycans that are specifically
affected by the EXT mutations.
The following model has been developed to account for the aberrant
chondrocyte proliferation and bone growth in the growth plate
(Figure 2).
how mutations affect the EXT protein levels and the chondrocyte
function.
Immunocytochemistry using EXT1 and EXT2 antibodies identified
significantly diminished levels of EXT1 and EXT2
proteins.Furthermore, exostosis chondrocytes have a unique
stellate appearance with elongated inclusions in the cytoplasm
composed of actin bundled by 1.5-mm repeat crossbridges of
a-actinin.
The exostosis chondrocytes produce aberrantly high levels of
muscle-specific a-actin, while b-actin levels are similar to normal
chondrocytes.
Altogether, these findings suggest that mutations in the EXT genes
affect the proteins regulating chondrocyte signaling. Our studies are
focused on identifying the proteoglycans that are specifically
affected by the EXT mutations.
The following model has been developed to account for the aberrant
chondrocyte proliferation and bone growth in the growth plate
(Figure 2).
Figure 2. Future studies will be
aimed at gaining a better
understanding of normal
mechanisms of bone growth which
may provide insights that will lead
to nonsurgical intervention in HME.
aimed at gaining a better
understanding of normal
mechanisms of bone growth which
may provide insights that will lead
to nonsurgical intervention in HME.
For more information on exostoses development please
click researchers names tabs located on the tool bar
click researchers names tabs located on the tool bar
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| Exostoses Development Section |
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| What is a chondrocyte |
Chondrocytes (from Greek chondros cartilage + kytos cell) are the only cells found in cartilage.
They produce and maintain the cartilaginous matrix, which consists mainly of collagen and
proteoglycans.
They produce and maintain the cartilaginous matrix, which consists mainly of collagen and
proteoglycans.
The MHE Research Foundation would like to thank Craig W. Wiesenhutter, M.D., U.C.L.A.
Rheumatology Pathophysiology of Disease Course for the use of this Chondrocyte animation.
There also other OSTEOARTHRITIS: SLIDES & ANIMATIONS and information contained on this
website http://www.cdaarthritis.com/OA/INDEX.HTM This maybe of interest to people with MHE as
they can develop early on set of osteoarthritis as a secondary complication of their MHE.
Rheumatology Pathophysiology of Disease Course for the use of this Chondrocyte animation.
There also other OSTEOARTHRITIS: SLIDES & ANIMATIONS and information contained on this
website http://www.cdaarthritis.com/OA/INDEX.HTM This maybe of interest to people with MHE as
they can develop early on set of osteoarthritis as a secondary complication of their MHE.
Osteochondroma / Exostoses Out Line: Link Click Here (*****You should read these papers,
when you would like to understand MHE / MO / HME research better*****)
when you would like to understand MHE / MO / HME research better*****)
Slide: Jeffrey D Esko, Phd
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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
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
The MHE Research Foundation is proud to be working with the EuroBoNeT consortium, a European Commission
granted Network of Excellence for studying the pathology and genetics of bone tumors.
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