Structural requirements for the action of parathyroid hormone-related protein (PTHrP) on bone resorption by isolated osteoclasts

Journal Article · Mon Dec 31 23:00:00 EST 1990 · Journal of Bone and Mineral Research; (United States)

DOI:https://doi.org/10.1002/jbmr.5650060114· OSTI ID:5595653

Evely, R S; Bonomo, A; Schneider, H G; Moseley, J M; Gallagher, J; Martin, T J ^[1]

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1. St. Vincent's Institute of Medical Research, Melbourne (Australia)

Parathyroid hormone-related protein (PTHrP) plays a major role in the syndrome of humoral hypercalcemia of malignancy (HHM) by its actions on bone and kidney. In this study an isolated osteoclast bone resorption assay was used to investigate the actions of this peptide and the structure-activity relationships for its resorption effect. As with PTH, neither synthetic nor recombinant PTHrP preparations stimulated resorption within highly purified osteoclast populations. Resorption was stimulated only in the presence of contaminating osteoblasts or in cocultures with the osteoblast-like cell line UMR-106. In the presence of osteoblasts PTHrP-(1-34) and PTHrP-(1-84) stimulated bone resorption in a dose-dependent manner with a potency comparable to that of PTH-(1-34) on a molar basis. The biologic activity of the PTHrP was shown to reside in the first 34 amino acids, and within that region the structural requirements for promotion of osteoclastic resorption resembled closely those for promotion of cyclic AMP formation in osteoblast-like cells. Using emulsion autoradiography with iodinated PTHrP-(1-34) and PTHrP-(1-84) on mixed bone cell preparations from neonatal rats, specific binding was demonstrated only to osteoblasts, not to osteoclasts. These results clearly demonstrate that PTHrP is a potent stimulator of bone resorption and that these effects are, like those of PTH, mediated by initial actions upon cells of the osteoblast lineage.

• OSTI ID: 5595653
• Journal Information: Journal of Bone and Mineral Research; (United States), Journal Name: Journal of Bone and Mineral Research; (United States) Vol. 6:1; ISSN JBMRE; ISSN 0884-0431
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
BODY
BONE CELLS
CALCIUM
CONNECTIVE TISSUE CELLS
DENSITY
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
ENDOCRINE GLANDS
GLANDS
IN VITRO
IODINE ISOTOPES
ISOTOPES
MAMMALS
METALS
ORGANIC COMPOUNDS
ORGANS
PARATHYROID GLANDS
PEPTIDES
PHYSICAL PROPERTIES
PROTEINS
RATS
RODENTS
SKELETON
SOMATIC CELLS
SORPTION
STRUCTURE-ACTIVITY RELATIONSHIPS
VERTEBRATES