CARBOXYL-TERMINAL PARATHYROID-HORMONE FRAGMENTS STIMULATE OSTEOCLAST-LIKE CELL-FORMATION AND OSTEOCLASTIC ACTIVITY

被引:59
作者
KAJI, H [1 ]
SUGIMOTO, T [1 ]
KANATANI, M [1 ]
MIYAUCHI, A [1 ]
KIMURA, T [1 ]
SAKAKIBARA, S [1 ]
FUKASE, M [1 ]
CHIHARA, K [1 ]
机构
[1] PEPTIDE INST INC,PROT RES FDN,OSAKA 562,JAPAN
关键词
D O I
10.1210/en.134.4.1897
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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(3-84), 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 weil 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.
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页码:1897 / 1904
页数:8
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