A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts.
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.
Department of Medicine, University of Western Australia, Fremantle Hospital.
A J
AJ
Fenton
B E
BE
Kemp
G N
GN
Kent
J M
JM
Moseley
M H
MH
Zheng
D J
DJ
Rowe
J M
JM
Britto
T J
TJ
Martin
G C
GC
Nicholson
D000595:Amino Acid Sequence; D000818:Animals; D001862:Bone Resorption; D002478:Cells, Cultured; D003584:Cytological Techniques; D003593:Cytoplasm / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C071097:parathyroid hormone-related protein (107-139)