Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair.
A number of proteins have recently been identified which play roles in regulating bone development. One important example is Indian hedgehog (Ihh) which is secreted by the prehyprtrophic chondrocytes. Ihh acts as an activator of a second secreted factor, parathyroid hormone-related protein (PTHrP), which, in turn, negatively regulates the rate of chondrocyte differentiation. Here we examine the expression of these genes and their molecular targets during different stages of bone development. In addition to regulating PTHrP expression in the perichondrium, we find evidence that Ihh may also act on the chondrocytes themselves at particular stages. As bone growth continues postnatally in mammals and the developmental process is reactivated during fracture repair, understanding the molecular basis regulating bone development is of medical relevance. We find that the same molecules that regulate embryonic endochondral ossification are also expressed during postnatal bone growth and fracture healing, suggesting that these processes are controlled by similar mechanisms.
Vortkamp
A
A
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Pathi
S
S
Peretti
G M
GM
Caruso
E M
EM
Zaleske
D J
DJ
Tabin
C J
CJ
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D001846:Bone Development / Q000235:genetics*; D002356:Cartilage / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002642:Chick Embryo; D004627:Embryonic Induction / Q000235:genetics; D017102:Fracture Healing / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D044162:Parathyroid Hormone-Related Protein; D000072079:Patched Receptors; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators
D053823:Hedgehog Proteins; D008565:Membrane Proteins; D044162:Parathyroid Hormone-Related Protein; D000072079:Patched Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators