Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone.
Indian hedgehog (Ihh) is essential for chondrocyte and osteoblast proliferation/differentiation during prenatal endochondral bone formation. The early lethality of various Ihh-ablated mutant mice, however, prevented further analysis of its role in postnatal bone growth and development. In this study, we describe the generation and characterization of a mouse model in which the Ihh gene was successfully ablated from postnatal chondrocytes in a temporal/spatial-specific manner; postnatal deletion of Ihh resulted in loss of columnar structure, premature vascular invasion, and formation of ectopic hypertrophic chondrocytes in the growth plate. Furthermore, destruction of the articular surface in long bones and premature fusion of growth plates of various endochondral bones was evident, resulting in dwarfism in mutant mice. More importantly, these mutant mice exhibited continuous loss of trabecular bone over time, which was accompanied by reduced Wnt signaling in the osteoblastic cells. These results demonstrate, for the first time, that postnatal chondrocyte-derived Ihh is essential for maintaining the growth plate and articular surface and is required for sustaining trabecular bone and skeletal growth.
Maeda
Yukiko
Y
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Nakamura
Eiichiro
E
Nguyen
Minh-Thanh
MT
Suva
Larry J
LJ
Swain
Frances L
FL
Razzaque
Mohammed S
MS
Mackem
Susan
S
Lanske
Beate
B
D000818:Animals; D019902:Chondrocytes / Q000378:metabolism*; D017931:DNA Primers; D017353:Gene Deletion; D006132:Growth Plate / Q000254:growth & development* / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010006:Osteoblasts / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D017931:DNA Primers; D053823:Hedgehog Proteins; C514061:ihh protein, mouse