The Indian Hedgehog - PTHrP System in Bone Development
199
Ihh
Fig. 3. The genes of the IhhIPTHrP feedback loop are expressed during fracture repair. In situ hybridization shows the expression of Ihh, PTHIPTHrP receptor, Pte, and Col-X in the cartilage callus on day 7 after the induction of the
fracture
11.5 Interaction of Ihh and BMP Signaling
11.5.1 BMP Expression During Chondrocyte Differentiation
To gain deeper insight into the process of endochondral ossification one
has to appreciate how the IhhlPTHrP signaling pathway interacts with
other signals regulating bone development. Bone morphogenetic proteins (BMPs), a subgroup of the conserved TGF-~ superfamily of secreted proteins (Hogan 1996; Kingsley 1994a; Kingsley 1994b), are
another group of signaling molecules that have been implicated in
regulating bone formation. During the early stages of bone development, BMP genes and their receptors are expressed in distinct cell types
within the cartilage elements. For example, BMP2, BMP4, BMP5, and
BMP7 are expressed in the perichondrium surrounding the skeletal
elements (Jones et al. 1991; Kingsley 1994b; Lyons et al. 1990; Zou et
al. 1997), whereas BMP6 and the BMP receptor IA (BMPR-IA) are
expressed in the hypertrophic and prehypertrophic chondrocytes
(Kawakami et al. 1996; Kingsley 1994a; Vortkamp et al. 1996).
199
Ihh
Fig. 3. The genes of the IhhIPTHrP feedback loop are expressed during fracture repair. In situ hybridization shows the expression of Ihh, PTHIPTHrP receptor, Pte, and Col-X in the cartilage callus on day 7 after the induction of the
fracture
11.5 Interaction of Ihh and BMP Signaling
11.5.1 BMP Expression During Chondrocyte Differentiation
To gain deeper insight into the process of endochondral ossification one
has to appreciate how the IhhlPTHrP signaling pathway interacts with
other signals regulating bone development. Bone morphogenetic proteins (BMPs), a subgroup of the conserved TGF-~ superfamily of secreted proteins (Hogan 1996; Kingsley 1994a; Kingsley 1994b), are
another group of signaling molecules that have been implicated in
regulating bone formation. During the early stages of bone development, BMP genes and their receptors are expressed in distinct cell types
within the cartilage elements. For example, BMP2, BMP4, BMP5, and
BMP7 are expressed in the perichondrium surrounding the skeletal
elements (Jones et al. 1991; Kingsley 1994b; Lyons et al. 1990; Zou et
al. 1997), whereas BMP6 and the BMP receptor IA (BMPR-IA) are
expressed in the hypertrophic and prehypertrophic chondrocytes
(Kawakami et al. 1996; Kingsley 1994a; Vortkamp et al. 1996).