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Calcified Tissue International
Published in: Calcified Tissue International 5/2006

01-11-2006

Transient Exposure to PTHrP (107-139) Exerts Anabolic Effects through Vascular Endothelial Growth Factor Receptor 2 in Human Osteoblastic Cells In Vitro

Authors: A. R. de Gortázar, V. Alonso, M. V. Alvarez-Arroyo, P. Esbrit

Published in: Calcified Tissue International | Issue 5/2006

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Abstract

Intermittent administration of the N-terminal fragment of parathyroid hormone (PTH) and PTH-related protein (PTHrP) induces bone anabolic effects. However, the effects of the C-terminal domain of PTHrP on bone turnover remain controversial. We examined the putative mechanisms whereby this PTHrP domain can affect osteoblastic differentiation, using human osteosarcoma MG-63 cells and osteoblastic cells from human trabecular bone. Intermittent exposure to PTHrP (107-139), within 10-100 nM, for only ≤24 hours during cell growth stimulated alkaline phosphatase (ALP) and Runt homology domain protein (Runx2) activities as well as osteocalcin (OC) and osteoprotegerin (OPG) expression but inhibited receptor activator of nuclear factor κB (NF-κB) ligand. Continuous exposure to this PTHrP peptide reversed these effects. The stimulatory effects of transient treatment with PTHrP (107-139) on OC mRNA and/or OPG protein expression were unaffected by a neutralizing anti-insulin-like growth factor I antibody or [Asn10, Leu11, d-Trp12]PTHrP (7-34) in these cells. On the other hand, the former antibody and the latter PTHrP antagonist abrogated the PTHrP (1-36)-induced increase in these osteoblastic products. Transient exposure to PTHrP (107-139), in contrast to PTHrP (1-36), stimulated vascular endothelial growth factor receptor 2 (VEGFR2) mRNA levels in these cells. Moreover, induction of ALP activity as well as OC and OPG expression by PTHrP (107-139) was blunted by SU5614, a permeable tyrosine kinase inhibitor of VEGFR2. Protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors abolished the PTHrP (107-139)-stimulated VEGFR2 and OPG mRNA levels in these cells. These results indicate that intermittent exposure to PTHrP (107-139) exerts potential anabolic effects through the PKC/ERK pathway and, subsequently, VEGFR2 upregulation in vitro in human osteoblastic cells.
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Metadata
Title
Transient Exposure to PTHrP (107-139) Exerts Anabolic Effects through Vascular Endothelial Growth Factor Receptor 2 in Human Osteoblastic Cells In Vitro
Authors
A. R. de Gortázar
V. Alonso
M. V. Alvarez-Arroyo
P. Esbrit
Publication date
01-11-2006
Publisher
Springer-Verlag
Published in
Calcified Tissue International / Issue 5/2006
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-006-0099-y

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