PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth.
The PTH/PTHrP receptor binds to two ligands with distinct functions: the calcium-regulating hormone, parathyroid hormone (PTH), and the paracrine factor, PTH-related protein (PTHrP). Each ligand, in turn, is likely to activate more than one receptor. The functions of the PTH/PTHrP receptor were investigated by deletion of the murine gene by homologous recombination. Most PTH/PTHrP receptor (-/-) mutant mice died in mid-gestation, a phenotype not observed in PTHrP (-/-) mice, perhaps because of the effects of maternal PTHrP. Mice that survived exhibited accelerated differentiation of chondrocytes in bone, and their bones, grown in explant culture, were resistant to the effects of PTHrP and Sonic hedgehog. These results suggest that the PTH/PTHrP receptor mediates the effects of Indian Hedgehog and PTHrP on chondrocyte differentiation.
Lanske
B
B
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Karaplis
A C
AC
Lee
K
K
Luz
A
A
Vortkamp
A
A
Pirro
A
A
Karperien
M
M
Defize
L H
LH
Ho
C
C
Mulligan
R C
RC
Abou-Samra
A B
AB
Jüppner
H
H
Segre
G V
GV
Kronenberg
H M
HM
D000818:Animals; D001846:Bone Development; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003001:Cloning, Molecular; D046508:Culture Techniques; D005246:Feedback; D017353:Gene Deletion; D018390:Gene Targeting; D006132:Growth Plate / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology / Q000502:physiology; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells; D015534:Trans-Activators
D053823:Hedgehog Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D015534:Trans-Activators