This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lanske, B. Articles by Kronenberg, H. M. Search for Related Content PubMed PubMed Citation Articles by Lanske, B. Articles by Kronenberg, H. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB PARATHYROID HORMONE

The Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Mediates Actions of Both Ligands in Murine Bone¹

Endocrine Unit (B.L., P.D., C.S.K., A.P., F.R.B., H.M.K.), Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114; Department of Orthopedic Surgery (W.J.L.), Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Arthritis Unit (S.M.K.), Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Henry M. Kronenberg, M.D., Endocrine Unit, Wellman 5, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: kronenberg.henry{at}mgh.harvard.edu

PTH and PTH-related peptide (PTHrP) have been shown to bind to and activate the same PTH/PTHrP receptor. Recent studies have demonstrated, however, the presence of additional receptors specific for each ligand. We used the PTHrP and PTH/PTHrP receptor gene knock-out models to investigate whether this receptor mediates the actions of both ligands in bone.

The similar phenotype of the PTHrP (-/-) and PTH/PTHrP receptor (-/-) animals in the growth plate of the tibia suggests that this receptor mediates the actions of PTHrP. Electron microscopic studies have confirmed the accelerated differentiation and disordered organization of chondrocytes, with the accumulation of large amounts of dispersed glycogen granules in the cytoplasm of proliferative and maturing cells of both genotypes.

The contrasting growth plate mineralization patterns of the PTHrP (-/-) and PTH/PTHrP receptor (-/-) mice, however, suggest that the actions of PTHrP and the PTH/PTHrP receptor are not identical.

Studies using calvariae from PTH/PTHrP receptor (-/-) embryos demonstrate that this receptor solely mediates the ability of PTH and PTHrP to stimulate adenylate cyclase in bone and to stimulate bone resorption.

Furthermore, we show that osteoblasts of PTH/PTHrP receptor (-/-) animals, but not PTHrP (-/-) animals, have decreased levels of collagenase 3, osteopontin, and osteocalcin messenger RNAs.

The PTH/PTHrP receptor, therefore, mediates distinct physiologic actions of both PTH and PTHrP.

This article has been cited by other articles:

				J. R. Hens, P. Dann, J.-P. Zhang, S. Harris, G. W. Robinson, and J. Wysolmerski BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction Development, March 15, 2007; 134(6): 1221 - 1230. [Abstract] [Full Text] [PDF]

				D. Sitara, M. S. Razzaque, R. St-Arnaud, W. Huang, T. Taguchi, R. G. Erben, and B. Lanske Genetic Ablation of Vitamin D Activation Pathway Reverses Biochemical and Skeletal Anomalies in Fgf-23-Null Animals Am. J. Pathol., December 1, 2006; 169(6): 2161 - 2170. [Abstract] [Full Text] [PDF]

				H. Baribault, J. Danao, J. Gupte, L. Yang, B. Sun, W. Richards, and H. Tian The G-Protein-Coupled Receptor GPR103 Regulates Bone Formation Mol. Cell. Biol., January 15, 2006; 26(2): 709 - 717. [Abstract] [Full Text] [PDF]

				E Gomez-Barrena, O Sanchez-Pernaute, R Largo, E Calvo, P Esbrit, and G Herrero-Beaumont Sequential changes of parathyroid hormone related protein (PTHrP) in articular cartilage during progression of inflammatory and degenerative arthritis Ann Rheum Dis, August 1, 2004; 63(8): 917 - 922. [Abstract] [Full Text] [PDF]

				B. Demiralp, H.-L. Chen, A. J. Koh, E. T. Keller, and L. K. McCauley Anabolic Actions of Parathyroid Hormone during Bone Growth Are Dependent on c-fos Endocrinology, October 1, 2002; 143(10): 4038 - 4047. [Abstract] [Full Text] [PDF]

				H. A. W. Tawfeek, F. Qian, and A. B. Abou-Samra Phosphorylation of the Receptor for PTH and PTHrP Is Required for Internalization and Regulates Receptor Signaling Mol. Endocrinol., January 1, 2002; 16(1): 1 - 13. [Abstract] [Full Text] [PDF]

				D. W. Soegiarto, S. Kiachopoulos, E. Schipani, H. Juppner, R. G. Erben, and B. Lanske Partial Rescue of PTH/PTHrP Receptor Knockout Mice by Targeted Expression of the Jansen Transgene Endocrinology, December 1, 2001; 142(12): 5303 - 5310. [Abstract] [Full Text] [PDF]

				P. J. Kostenuik, C. Capparelli, S. Morony, S. Adamu, G. Shimamoto, V. Shen, D. L. Lacey, and C. R. Dunstan OPG and PTH-(1-34) Have Additive Effects on Bone Density and Mechanical Strength in Osteopenic Ovariectomized Rats Endocrinology, October 1, 2001; 142(10): 4295 - 4304. [Abstract] [Full Text] [PDF]

				S. C. Garner, M. Pi, Q. Tu, and L. D. Quarles Rickets in Cation-Sensing Receptor-Deficient Mice: An Unexpected Skeletal Phenotype Endocrinology, September 1, 2001; 142(9): 3996 - 4005. [Abstract] [Full Text] [PDF]

				N. Selvamurugan, M. R. Pulumati, D. R. Tyson, and N. C. Partridge Parathyroid Hormone Regulation of the Rat Collagenase-3 Promoter by Protein Kinase A-dependent Transactivation of Core Binding Factor alpha 1 J. Biol. Chem., February 18, 2000; 275(7): 5037 - 5042. [Abstract] [Full Text] [PDF]