Endocrinology, Vol 129, 1762-1768, Copyright © 1991 by Endocrine Society

ARTICLES

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

AJ Fenton, BE Kemp, GN Kent, JM Moseley, MH Zheng, DJ Rowe, JM Britto, TJ Martin and GC Nicholson
Department of Medicine, University of Western Australia, Fremantle Hospital.

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.