Multiple Aspects of Ihh Signaling in the Endochondral Skeleton
Abstract 2005 MHE Conference
Matthew Hilton,PH.D.
Department of Internal Medicine, Division of Bone &
Mineral Diseases Washington University School of Medicine St. Louis, MO 63110
Indian hedgehog (Ihh) is indispensable for proper endochondral bone development. In the developing cartilage, Ihh expressed
in the prehypertrophic and early hypertrophic chondrocytes signals through chondrocytes and the perichondrium to regulate
chondrocyte proliferation and hypertrophy.
Previous studies have shown that Ihh on one hand directly regulates chondrocyte proliferation, and on the other hand indirectly
controls chondrocyte maturation through regulation of Parathyroid hormone like hormone (Pthlh). However, it has not been
understood 1) how Ihh transports through the cartilage, and 2) whether Ihh directly controls pthlh expression.
Our recent studies with Exostosin1 (Ext1) heterozygous mice, supports that heparan sulfate synthesis normally restricts the
transportation of Ihh within the growth plate cartilage.
More recently, through localized removal of Smoothened (Smo), the key mediator of hedgehog signaling, using a tamoxifen
inducible Col2Cre transgenic mouse, we demonstrated that Ihh directly regulates pthlh expression in the immature articular
chondrocytes. Additionally, we uncovered that Ihh may directly regulate the organization of columnar chondrocytes in a
Pthlh-independent manner.
Abstract 2005 MHE Conference
Matthew Hilton,PH.D.
Department of Internal Medicine, Division of Bone &
Mineral Diseases Washington University School of Medicine St. Louis, MO 63110
Indian hedgehog (Ihh) is indispensable for proper endochondral bone development. In the developing cartilage, Ihh expressed
in the prehypertrophic and early hypertrophic chondrocytes signals through chondrocytes and the perichondrium to regulate
chondrocyte proliferation and hypertrophy.
Previous studies have shown that Ihh on one hand directly regulates chondrocyte proliferation, and on the other hand indirectly
controls chondrocyte maturation through regulation of Parathyroid hormone like hormone (Pthlh). However, it has not been
understood 1) how Ihh transports through the cartilage, and 2) whether Ihh directly controls pthlh expression.
Our recent studies with Exostosin1 (Ext1) heterozygous mice, supports that heparan sulfate synthesis normally restricts the
transportation of Ihh within the growth plate cartilage.
More recently, through localized removal of Smoothened (Smo), the key mediator of hedgehog signaling, using a tamoxifen
inducible Col2Cre transgenic mouse, we demonstrated that Ihh directly regulates pthlh expression in the immature articular
chondrocytes. Additionally, we uncovered that Ihh may directly regulate the organization of columnar chondrocytes in a
Pthlh-independent manner.
Research authored by Hilton
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
| Dr. Hilton's research |
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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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