Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like cell formation and osteoclastic activity.
The controversy still exists about the biological activity of carboxyl (C)-terminal PTH fragments. The present study was performed to examine the effect of C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing activity. In contrast to human (h) PTH-(1-34) or hPTH-(1-84), any C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84), and hPTH-(69-84)] did not affect cellular cAMP production and intracellular calcium in osteoblastic UMR-106 cells. Although hPTH-(1-84) caused an increase in cAMP production and intracellular calcium less effectively than hPTH-(1-34) in UMR-106 cells, the former caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than the latter. All of the C-terminal fragments significantly stimulated osteoclast-like cell formation, and their effectiveness seemed to depend on the amino acid length of the fragments. The conditioned medium from UMR-106 cells pretreated with C-terminal PTH as well as amino-terminal PTH significantly stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Moreover, all of the C-terminal fragments stimulated osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts, and their effectiveness seemed to depend on the length of fragments. As for bone-resorbing activity by mature osteoclasts, all of the C-terminal fragments stimulated bone resorption in osteoblast-containing mouse bone cell cultures, whereas these fragments did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The present study first indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity by mature osteoclasts in the presence of osteoblasts and accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.
Kaji
H
H
Department of Medicine, Kobe University School of Medicine, Japan.
Sugimoto
T
T
Kanatani
M
M
Miyauchi
A
A
Kimura
T
T
Sakakibara
S
S
Fukase
M
M
Chihara
K
K
D000818:Animals; D001862:Bone Resorption; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D016922:Cellular Senescence / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C023443:carboxyl-terminal parathyroid hormone; D000242:Cyclic AMP; D002118:Calcium