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Endocrinology, Vol 131, 2742-2746, Copyright © 1992 by Endocrine Society

ARTICLES

Human parathyroid hormone-related peptide-(107-111) does not inhibit bone resorption in neonatal mouse calvariae

T Sone, H Kohno, H Kikuchi, T Ikeda, R Kasai, Y Kikuchi, R Takeuchi, J Konishi and C Shigeno
Department of Radiology and Nuclear Medicine, Kyoto University Hospital, Japan.

Recent analysis of the structure-function relationship of human PTH- related peptide (hPTHrP) has led to the discovery that its direct inhibitory activity on osteoclastic bone resorption resides fully in the 107-111 sequence of the peptide, as assessed by a bone resorption assay using isolated rat osteoclasts. Here we report that hPTHrP-(107- 111) is inactive in neonatal mouse calvariae in culture. hPTHrP-(107- 111), at doses of 10(-12)-10(-6) M and incubation periods up to 96 h, did not affect either basal or agonist-stimulated 45Ca release from prelabeled neonatal mouse calvariae, while salmon calcitonin was a potent and powerful inhibitor of both basal and stimulated 45Ca release from bone. Moreover, salmon calcitonin, but not hPTHrP-(107-111), inhibited the increase in osteoclast number in hPTHrP-(1-34)-treated bones. Furthermore, hPTHrP-(107-139) also failed to inhibit 45Ca release and the hPTHrP-(1-34)-induced increase in osteoclast number in this organ culture model when tested under conditions identical to those for hPTHrP-(107-111). The addition of indomethacin to hPTHrP-(107- 111)- or hPTHrP-(107-139)-treated bones was without effect, excluding the possibility that the direct inhibitory activity of these peptides on osteoclasts is ablated by a prostaglandin-mediated mechanism. Although the mechanism underlying the apparent inability of the carboxyl-terminal PTHrP fragments to inhibit osteoclastic bone resorption in neonatal mouse calvariae is unknown, it may involve the complex microenvironment of osteoclasts in intact bone, which contains a large variety of cell types other than osteoclasts.


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Copyright © 1992 by The Endocrine Society