Human parathyroid hormone-related peptide-(107-111) does not inhibit bone resorption in neonatal mouse calvariae
| Autor: | Junji Konishi, Yuko Kikuchi, Ryo Takeuchi, Toshihiko Ikeda, Chohei Shigeno, Hiroaki Kohno, Haruki Kikuchi, Ryuichi Kasai, Teruki Sone |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
musculoskeletal diseases
Calcitonin medicine.medical_specialty Ratón Indomethacin Parathyroid hormone Osteoclasts Biology Organ culture Bone resorption Bone and Bones Mice Endocrinology Organ Culture Techniques Osteoclast Internal medicine medicine Animals Humans Bone Resorption Parathyroid hormone-related protein Calcium Radioisotopes Parathyroid Hormone-Related Protein Proteins Peptide Fragments Resorption medicine.anatomical_structure Animals Newborn Parathyroid Hormone Calcium |
| Zdroj: | Endocrinology. 131(6) |
| ISSN: | 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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