title: Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development.
abstract: Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized. One early phenotype is shared by both knockouts. Normally, the first chondrocytes to become hypertrophic are located in the centers of long bones; this polarity is greatly diminished in both these knockouts. The PTH/PTHrP receptor-deficient (PTH/PTHrP-R(-/-)) mice exhibited 2 unique phenotypes not shared by the PTHrP(-/-) mice. During intramembranous bone formation in the shafts of long bones, only the PTH/PTHrP-R(-/-) bones exhibit a striking increase in osteoblast number and matrix accumulation. Furthermore, the PTH/PTHrP-R(-/-) mice showed a dramatic decrease in trabecular bone formation in the primary spongiosa and a delay in vascular invasion of the early cartilage model. In the double-homozygous knockout mice, the delay in vascular invasion did not occur. Thus, PTHrP must slow vascular invasion by a mechanism independent of the PTH/PTHrP receptor.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lanske
authors.forename: M
authors.initials: M
authors.lastname: Amling
authors.forename: L
authors.initials: L
authors.lastname: Neff
authors.forename: J
authors.initials: J
authors.lastname: Guiducci
authors.forename: R
authors.initials: R
authors.lastname: Baron
authors.forename: H M
authors.initials: HM
authors.lastname: Kronenberg
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics* / Q000502:physiology*; D001842:Bone and Bones / Q000002:abnormalities* / Q000098:blood supply; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein; D010641:Phenotype; D011247:Pregnancy; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics* / Q000502:physiology*
chemical_list: D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone