Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

Kelly Lenton, Aaron James, Alina Manu, Samantha A. Brugmann, Daniel Birker, Emily R. Nelson, Philipp Leucht, Jill A. Helms, Michael T. Longaker

Research output: Contribution to journalArticle

Abstract

Much is known regarding the role of Indian hedgehog (Ihh) in endochondral ossification, where Ihh regulates multiple steps of chondrocyte differentiation. The Ihh -/- phenotype is most notable for severely foreshortened limbs and a complete absence of mature osteoblasts. A far less explored phenotype in the Ihh -/- mutant is found in the calvaria, where bones form predominately through intramembranous ossification. We investigated the role of Ihh in calvarial bone ossification, finding that proliferation was largely unaffected. Instead, our results indicate that Ihh is a pro-osteogenic factor that positively regulates intramembranous ossification. We confirmed through histologic and quantitative gene analysis that loss of Ihh results in reduction of cranial bone size and all markers of osteodifferentiation. Moreover, in vitro studies suggest that Ihh loss reduces Bmp expression within the calvaria, an observation that may underlie the Ihh -/- calvarial phenotype. In conjunction with the newly recognized roles of Hedgehog deregulation in craniosynostosis, our study defines Ihh as an important positive regulator of cranial bone ossification.

Original languageEnglish (US)
Pages (from-to)784-796
Number of pages13
JournalGenesis
Volume49
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

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Bone Morphogenetic Proteins
Osteogenesis
Bone and Bones
Phenotype
Skull
Craniosynostoses
Chondrocytes
Osteoblasts
Extremities
Observation
Genes

Keywords

  • Chondrogenesis
  • Osteogenesis
  • Skeletal
  • Suture

ASJC Scopus subject areas

  • Endocrinology
  • Cell Biology
  • Genetics

Cite this

Lenton, K., James, A., Manu, A., Brugmann, S. A., Birker, D., Nelson, E. R., ... Longaker, M. T. (2011). Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. Genesis, 49(10), 784-796. https://doi.org/10.1002/dvg.20768

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. / Lenton, Kelly; James, Aaron; Manu, Alina; Brugmann, Samantha A.; Birker, Daniel; Nelson, Emily R.; Leucht, Philipp; Helms, Jill A.; Longaker, Michael T.

In: Genesis, Vol. 49, No. 10, 10.2011, p. 784-796.

Research output: Contribution to journalArticle

Lenton, K, James, A, Manu, A, Brugmann, SA, Birker, D, Nelson, ER, Leucht, P, Helms, JA & Longaker, MT 2011, 'Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling', Genesis, vol. 49, no. 10, pp. 784-796. https://doi.org/10.1002/dvg.20768
Lenton, Kelly ; James, Aaron ; Manu, Alina ; Brugmann, Samantha A. ; Birker, Daniel ; Nelson, Emily R. ; Leucht, Philipp ; Helms, Jill A. ; Longaker, Michael T. / Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. In: Genesis. 2011 ; Vol. 49, No. 10. pp. 784-796.
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