Stimulatory effect of carboxyl-terminal parathyroid hormone fragments on osteoclast-like cell formation and osteoclastic activity

The controversy exists about the biological activity of carboxyl (C)-terminal parathyroid hormone (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. Human (h) PTH-(1-84) caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than hPTH-(1-34). All of the C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84) and hPTH-(69-84)] significantly stimulated osteoclast-like cell formation. The conditioned medium from osteoblastic 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 also caused a stimulation of osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts. As for bone-resorbing activity of mature osteoclasts, all of the C-terminal fragments stimulated bone-resorbing activity in osteoblast-containing mouse bone cell cultures, while these fragments did not affect bone-resorbing activity of isolated rabbit osteoclasts. The present study indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity of mature osteoclasts in the presence of osteoblast and also accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.