Carboxyl-terminal peptides from parathyroid hormone-related protein stimulate osteoclast-like cell formation.
The role of the carboxyl (C)-terminal portion of PTH-related protein (PTHrP) in bone resorption continues to be controversial. The present study was performed to examine the effect of C-terminal PTHrP peptides on osteoclast-like cell formation as well as bone resorption in mice. C-Terminal PTHrP peptides [human (h) PTHrP-(107-139) and hPTHrP-(107-111); 10(-10)-10(-8) M] stimulated osteoclast-like cell formation in a concentration-dependent manner in osteoblast-containing mouse bone cell cultures. Moreover, osteoclast-like cells newly formed by these peptides possessed the ability to form pits on the dentine slices. The conditioned medium from UMR-106 cells and MC3T3-E1 cells pretreated with the C-terminal peptides did not affect osteoclast-like cell formation from mouse hemopoietic blast cells derived from spleen cells. The C-terminal peptides as well as hPTHrP-(1-34) stimulated osteoclast-like cell formation from mouse hemopoietic blast cells in the absence of osteoblasts, although both amino- and C-terminal peptides were unable to support hemopoietic blast cells. Protein kinase-C inhibitors (H-7 and staurosporine) almost completely inhibited the stimulation of osteoclast-like cell formation by the C-terminal peptides in both the presence and absence of osteoblasts. The C-terminal peptides did not affect bone resorption by mature osteoclasts in osteoblast-containing mouse bone cell cultures. The present study indicates that C-terminal PTHrP peptides possess the ability to stimulate osteoclast-like cell formation in both the presence and absence of osteoblasts, possibly through the pathway involving protein kinase-C activation.
Kaji
H
H
Department of Medicine, Kobe University School of Medicine, Japan.
Sugimoto
T
T
Kanatani
M
M
Fukase
M
M
Chihara
K
K
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D002116:Calcitonin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C025497:parathyroid hormone (3-34) amide, Nle(8,18)-Nle(34)-; D002116:Calcitonin; D011493:Protein Kinase C