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A. Vortkamp
chondrocytes even if surrounded by proliferating wild-type cells. Therefore the PTHIPTHrP receptor acts cell autonomously and is furthermore
necessary to block chondrocyte differentiation (Chung et al. 1998).
Secondly, the authors found that although PTHIPTHrP receptor -/- mice
have severely shortened bones, chimeric mice show an enlargement of
the skeletal elements that is proportional to the degree of chimerism.
Morphological and molecular analysis revealed that in chimeric mice
premature hypertrophic differentiation of the PTH/PTHrP receptor -/cells results in a second zone of hypertrophic differentiation close to the
periarticular region. The differentiating chondrocytes express Ihh which
in turn induces the expression of increased levels of PTHrP in the joint
region. The elevated level of PTHtP is thought to induce a delay of
chondrocyte differentiation in wild-type celIs resulting in the observed
enlargement of the skeletal elements.
Summarizing, experiments both in chick and mice demonstrated that
Ihh and PTHrP interact to regulate chondrocyte differentiation. However, whether the interaction of Ihh and PTHrP is direct or indirect, and
how the Ihh signal is transmitted to the joint region to induce PTHrP has
still to be elucidated. Ptc as a receptor for Ihh seems to have an important function in this process and it is necessary to anal yze the role of the
two Ptc expression domains in regulating chondrocyte differentiation in
more detail to fully understand Ihh signaling.
11.4 The IhhlPTHrP Negative Feedback Loop Regulates
Postnatal Bone Growth and Fracture Repair
11.4.1 Postnatal Bone Growth
Endochondral ossification is not only an embryonic process, but continues until the proliferating chondrocytes are completely replaced by bone
and only articular cartilage remains at either end of the skeletal elements. Mice and other mammals differ slightly as they develop secondary ossification centers at the distal ends of the skeletal elements,
leaving a zone of proliferating and differentiating chondrocytes, the
epiphysial growth plate, in between the two ossification areas (Floyd et
a1. 1987). The growth plate is responsible for postnatal bone growth
A. Vortkamp
chondrocytes even if surrounded by proliferating wild-type cells. Therefore the PTHIPTHrP receptor acts cell autonomously and is furthermore
necessary to block chondrocyte differentiation (Chung et al. 1998).
Secondly, the authors found that although PTHIPTHrP receptor -/- mice
have severely shortened bones, chimeric mice show an enlargement of
the skeletal elements that is proportional to the degree of chimerism.
Morphological and molecular analysis revealed that in chimeric mice
premature hypertrophic differentiation of the PTH/PTHrP receptor -/cells results in a second zone of hypertrophic differentiation close to the
periarticular region. The differentiating chondrocytes express Ihh which
in turn induces the expression of increased levels of PTHrP in the joint
region. The elevated level of PTHtP is thought to induce a delay of
chondrocyte differentiation in wild-type celIs resulting in the observed
enlargement of the skeletal elements.
Summarizing, experiments both in chick and mice demonstrated that
Ihh and PTHrP interact to regulate chondrocyte differentiation. However, whether the interaction of Ihh and PTHrP is direct or indirect, and
how the Ihh signal is transmitted to the joint region to induce PTHrP has
still to be elucidated. Ptc as a receptor for Ihh seems to have an important function in this process and it is necessary to anal yze the role of the
two Ptc expression domains in regulating chondrocyte differentiation in
more detail to fully understand Ihh signaling.
11.4 The IhhlPTHrP Negative Feedback Loop Regulates
Postnatal Bone Growth and Fracture Repair
11.4.1 Postnatal Bone Growth
Endochondral ossification is not only an embryonic process, but continues until the proliferating chondrocytes are completely replaced by bone
and only articular cartilage remains at either end of the skeletal elements. Mice and other mammals differ slightly as they develop secondary ossification centers at the distal ends of the skeletal elements,
leaving a zone of proliferating and differentiating chondrocytes, the
epiphysial growth plate, in between the two ossification areas (Floyd et
a1. 1987). The growth plate is responsible for postnatal bone growth