PTHrP, PTH, and the PTH/PTHrP receptor in endochondral bone development.
Endochondral bone development is a fascinating story of proliferation, maturation, and death. An understanding of this process at the molecular level is emerging. In particular, significant advances have been made in understanding the role of parathyroid-hormone-related peptide (PTHrP), parathyroid hormone (PTH), and the PTH/PTHrP receptor in endochondral bone development. Mutations of the PTH/PTHrP receptor have been identified in Jansen metaphyseal chondrodysplasia, Blomstrand's lethal chondrodysplasia, and enchondromatosis. Furthermore, genetic manipulations of the PTHrP, PTH, and the PTH/PTHrP receptor genes, respectively, have demonstrated the critical role of these proteins in regulating both the switch between proliferation and differentiation of chondrocytes, and their replacement by bone cells. A future area of investigation will be the identification of downstream effectors of PTH, PTHrP, and PTH/PTHrP receptor activities. Furthermore, it will be of critical importance to study how these proteins cooperate and integrate with other molecules that are essential for growth plate development.
Schipani
Ernestina
E
Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA. schipani@helix.mgh.harvard.edu
Provot
Sylvain
S
D000818:Animals; D001846:Bone Development; D002454:Cell Differentiation; D019902:Chondrocytes / Q000502:physiology; D004392:Dwarfism / Q000235:genetics; D004687:Enchondromatosis / Q000235:genetics; D005260:Female; D006132:Growth Plate / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D010009:Osteochondrodysplasias / Q000235:genetics / Q000473:pathology; D010281:Parathyroid Hormone / Q000235:genetics / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000502:physiology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1