11 The Indian Hedgehog - PTHrP System
in Bone Development
A. Vortkamp
11.1
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 191
11.2 Indian Hedgehog Signaling During Chondrocyte Differentiation. 192
11.3 Ihh and PTHrP Interact in a Negative Feedback Loop
Regulating Chondrocyte Differentiation .................... 193
11.4 The IhhlPTHrP Negative Feedback Loop
Regulates Postnatal Bone Growth and Fracture Repair . . . . . . . .. 196
11.5 Interaction of Ihh and BMP Signaling .... . . . . . . . . . . . . . . . . .. 199
11.6 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205
11.1 Introduction
During embryonic development the bones of the vertebrate skeleton
develop by two different mechanisms. Most of the bones of the skull are
formed by intramembranous ossification in which mesenchymal cells
directly differentiate into osteoblasts. The second mechanism, called
endochondral ossification, is used to form the bones of the axial and
appendicular skeleton as well as some of the facial bones. Endochondral
ossification (Erlebacher et al. 1995; Hinchcliffe and Johnson 1980)
starts with mesenchymal cells that aggregate and differentiate into chondrocytes, thus forming cartilage elements which serve as templates for
the later bones. Cells in the middle of these cartilage elements start to
differentiate into hypertrophic chondrocytes, a step that is necessary for
the invasion of blood vessels and the subsequent replacement of carti-
in Bone Development
A. Vortkamp
11.1
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 191
11.2 Indian Hedgehog Signaling During Chondrocyte Differentiation. 192
11.3 Ihh and PTHrP Interact in a Negative Feedback Loop
Regulating Chondrocyte Differentiation .................... 193
11.4 The IhhlPTHrP Negative Feedback Loop
Regulates Postnatal Bone Growth and Fracture Repair . . . . . . . .. 196
11.5 Interaction of Ihh and BMP Signaling .... . . . . . . . . . . . . . . . . .. 199
11.6 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205
11.1 Introduction
During embryonic development the bones of the vertebrate skeleton
develop by two different mechanisms. Most of the bones of the skull are
formed by intramembranous ossification in which mesenchymal cells
directly differentiate into osteoblasts. The second mechanism, called
endochondral ossification, is used to form the bones of the axial and
appendicular skeleton as well as some of the facial bones. Endochondral
ossification (Erlebacher et al. 1995; Hinchcliffe and Johnson 1980)
starts with mesenchymal cells that aggregate and differentiate into chondrocytes, thus forming cartilage elements which serve as templates for
the later bones. Cells in the middle of these cartilage elements start to
differentiate into hypertrophic chondrocytes, a step that is necessary for
the invasion of blood vessels and the subsequent replacement of carti-