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Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling
Author(s) -
Lenton Kelly,
James Aaron W.,
Manu Alina,
Brugmann Samantha A.,
Birker Daniel,
Nelson Emily R.,
Leucht Philipp,
Helms Jill A.,
Longaker Michael T.
Publication year - 2011
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20768
Subject(s) - indian hedgehog , intramembranous ossification , endochondral ossification , calvaria , ossification , endocrinology , medicine , biology , chondrocyte , hedgehog , anatomy , microbiology and biotechnology , signal transduction , cartilage , genetics , in vitro
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. genesis 49:784–796, 2011. © 2011 Wiley‐Liss, Inc.