A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts.

Abstract

PTH-related protein (PTHrP) interacts, via its amino-terminal 34 residues, with PTH receptors on osteoblasts to stimulate osteoclastic bone resorption indirectly. We now report that mature hPTHrP-(1-141) (EC50, approximately 10(-11) M) and a carboxyl-terminal fragment, PTHrP-(107-139) (EC50, approximately 10(-15) M), are potent inhibitors of resorption in an isolated rat osteoclast bone resorption assay, whereas hPTHrP-(1-108) and hPTHrP-(1-34) are inactive in this respect. PTHrP-(107-139) also inhibits resorption in a rat long bone organ culture system and reduces osteoclast spreading. PTHrP-(107-139) does not act on osteoclasts via a cAMP signal transduction mechanism, but its effects may be mediated by protein kinase-C. This previously unrecognized action of PTHrP, to inhibit osteoclastic bone resorption directly, indicates that PTHrP may be a precursor of multiple biologically active peptides with differing physiological functions.

• Authors: A J Fenton, B E Kemp, G N Kent, J M Moseley, M H Zheng, D J Rowe, J M Britto, T J Martin, G C Nicholson
• Journal: Endocrinology (Endocrinology) Vol. 129 Issue 4 Pg. 1762-8 (Oct 1991) ISSN: 0013-7227 [Print] United States
• PMID: 1915066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Parathyroid Hormone-Related Protein
• Peptide Fragments
• Proteins
• parathyroid hormone-related protein (107-139)

Topics

• Amino Acid Sequence
• Animals
• Bone Resorption
• Cells, Cultured
• Cytological Techniques
• Cytoplasm (ultrastructure)
• Molecular Sequence Data
• Osteoclasts (drug effects, physiology, ultrastructure)
• Parathyroid Hormone-Related Protein
• Peptide Fragments (pharmacology)
• Proteins (pharmacology)
• Signal Transduction
• Time Factors
• Tumor Cells, Cultured