The biological action of parathyroid hormone-related peptide (PTHrP) and fibroblast growth factor receptor 3 (FGFR3) on bone and cartilage.
Parathyroid hormone (PTH)-related peptide (PTHrP) was determined to be a factor inducing malignancy-associated hypercalcemia by activating a common receptor (PTH/PTHrP receptor) with PTH. PTHrP gene "knock out" mice showed a form of dyschondroplasia due to reduced proliferation of chondrocytes. In addition, heterogenous populations of variously-differentiated chondrocytes were present in the hypertrophic zone of the mutant epiphyseal plate. Although the homozygotes die within several hours after birth, the adult mice, heterozygous for PTHrP gene deletion, showed a delayed skeletal abnormality at 3 month old, with a reduced amount of PTHrP transcript, therefore, PTHrP appears to modulate cell proliferation and differentiation at both fetal and adult stages. The co-localization of PTHrP and its receptor in osteoblastic cells and chondrocytes suggested a paracrine/autocine mode of action manner of these molecules. Recently, fibroblast growth factor receptor 3 (FGFR3) deficient mice demonstrated skeletal defects including kyphosis, scoliosis, crooked tails and curvature and overgrowth of long bones and vertebrae, which are caused by an increase in proliferation. Therefore, it seems that PTHrP and FGFR3 serve as positive and negative regulators on the chondrocyte proliferation, respectively. In this paper, we review our recent studies on the histological abnormality of long bone seen in PTHrP gene deficient- and FGFR3 gene deficient-mice.
Amizuka
N
N
Department of Oral Anatomy, Niigata University, Faculty of Dentistry, 5274, 2-Bancho, Gakkoucho-Dori, Niigata 951-8514, Japan.
Ozawa
H
H
Sasaki
T
T
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D019902:Chondrocytes / Q000166:cytology*; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology*; D010009:Osteochondrodysplasias / Q000209:etiology; D044162:Parathyroid Hormone-Related Protein; D011505:Protein-Tyrosine Kinases; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*
D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D017468:Receptors, Fibroblast Growth Factor; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3