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Research authored by Dr.Vortkamp
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
Ihh signaling in the growth plate.
Abstract 2005 MHE conference
Andrea Vortkamp
Centre for Medical Biotechnology, Department of Developmental
Biology, University Duisburg-Essen, 45117 Essen, Germany
Endochondral ossification is a multi step process during which a cartilage template is successively
replaced by bone tissue. Chondrocytes in the cartilage anlagen undergo several steps of
differentiation until they become terminal hypertrophic and are subsequently replaced by bone.
The secreted growth factor Indian hedgehog (Ihh) is expressed in a distinct population of
chondrocytes that undergo hypertrophic differentiation. Ihh interacts with a second secreted
molecule, Parathyroid Hormone related Protein (PTHrP), expressed in the distal ends of the cartilage
elements in a negative feedback mechanism to regulate the onset of hypertrophic
differentiation.Analyzing a mouse line carrying a hypomorphic allele of Ext1,a glycosytransferase
necessary for the synthesis of heparan sulfates (HS), we have recently shown that HS negatively
regulates the propagation of the Ihh signal in a concentration dependent manner. Our data strongly
indicate that Ihh acts as a long range morphogen directly inducing the expression of PTHrP.
To further investigate the interaction between Ihh and PTHrP, we have started to analyze the role of
the zinc finger transcription factor Gli3, which acts downstream of hedgehog signals in other organs.
Ihh;Gli3 double mutants indicate that Gli3 acts as a repressor downstream of Ihh in regulating
chondrocyte proliferation and the expression of PTHrP, and, thus, the onset of hypertrophic
differentiation.
Furthermore, our studies identified a new function of the Ihh/Gli3 system in negatively regulating the
differentiation of distal, low proliferating (zone) into central, high proliferating (zone II) chondrocytes.
Whereas the domain of zone II chondrocytes is determined by the level of PTHrP, the transition of
zone I into zone II chondrocytes is regulated by Gli3R independent of PTHrP.
Abstract 2005 MHE conference
Andrea Vortkamp
Centre for Medical Biotechnology, Department of Developmental
Biology, University Duisburg-Essen, 45117 Essen, Germany
Endochondral ossification is a multi step process during which a cartilage template is successively
replaced by bone tissue. Chondrocytes in the cartilage anlagen undergo several steps of
differentiation until they become terminal hypertrophic and are subsequently replaced by bone.
The secreted growth factor Indian hedgehog (Ihh) is expressed in a distinct population of
chondrocytes that undergo hypertrophic differentiation. Ihh interacts with a second secreted
molecule, Parathyroid Hormone related Protein (PTHrP), expressed in the distal ends of the cartilage
elements in a negative feedback mechanism to regulate the onset of hypertrophic
differentiation.Analyzing a mouse line carrying a hypomorphic allele of Ext1,a glycosytransferase
necessary for the synthesis of heparan sulfates (HS), we have recently shown that HS negatively
regulates the propagation of the Ihh signal in a concentration dependent manner. Our data strongly
indicate that Ihh acts as a long range morphogen directly inducing the expression of PTHrP.
To further investigate the interaction between Ihh and PTHrP, we have started to analyze the role of
the zinc finger transcription factor Gli3, which acts downstream of hedgehog signals in other organs.
Ihh;Gli3 double mutants indicate that Gli3 acts as a repressor downstream of Ihh in regulating
chondrocyte proliferation and the expression of PTHrP, and, thus, the onset of hypertrophic
differentiation.
Furthermore, our studies identified a new function of the Ihh/Gli3 system in negatively regulating the
differentiation of distal, low proliferating (zone) into central, high proliferating (zone II) chondrocytes.
Whereas the domain of zone II chondrocytes is determined by the level of PTHrP, the transition of
zone I into zone II chondrocytes is regulated by Gli3R independent of PTHrP.
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| About Dr. Vortkamp's research |
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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
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