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Matthew Hilton, PH.D.
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)
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Dr. Hilton'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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