Preptin, another peptide product of the pancreatic β-cell, is osteogenic in vitro and in vivo
- 1 January 2007
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 292 (1), E117-E122
- https://doi.org/10.1152/ajpendo.00642.2005
Abstract
Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted with insulin and amylin from the pancreatic β-cells. Preptin corresponds to Asp69-Leu102 of pro-IGF-II. Increased circulating levels of a pro-IGF-II peptide complexed with IGF-binding protein-2 have been implicated in the high bone mass phenotype observed in patients with chronic hepatitis C infection. We have assessed preptin's activities on bone. Preptin dose-dependently stimulated the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts and osteoblast-like cell lines at periphysiological concentrations (>10−11 M). In addition, thymidine incorporation was stimulated in murine neonatal calvarial organ culture, likely reflecting the proliferation of cells from the osteoblast lineage. Preptin did not affect bone resorption in this model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells in a dose-dependent manner (10−8-10−10 M), and its proliferative effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing the number of apoptotic cells by >20%. In vivo administration of preptin increased bone area and mineralizing surface in adult mice. These data demonstrate that preptin, which is cosecreted from the pancreatic β-cell with amylin and insulin, is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity.Keywords
This publication has 27 references indexed in Scilit:
- Nutrition-Related Peptides and Bone HomeostasisJournal of Bone and Mineral Research, 2006
- Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnoverBone, 2005
- Leptin deficiency—Lessons in regional differences in the regulation of bone massBone, 2004
- Relationships among body mass, its components, and boneBone, 2002
- Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet β-cells and enhances insulin secretionBiochemical Journal, 2001
- Lysophosphatidic Acid Is an Osteoblast Mitogen Whose Proliferative Actions Involve Gi Proteins and Protein Kinase C, But Not P42/44 Mitogen-Activated Protein KinasesEndocrinology, 2001
- A neuro (endo)crine regulation of bone remodelingBioEssays, 2000
- Leptin Inhibits Bone Formation through a Hypothalamic Relay: A Central Control of Bone MassCell, 2000
- Biophysical and Biological Properties of Naturally Occurring High Molecular Weight Insulin-like Growth Factor II VariantsOnline Journal of Public Health Informatics, 1997
- Amylin Stimulates Osteoblast Proliferation and Increases Mineralized Bone Volume in Adult MiceBiochemical and Biophysical Research Communications, 1995