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The neuropeptide VIP regulates the expression of osteoclastogenic factors in osteoblasts
Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
2011 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 112, no 12, 3732-3741 p.Article in journal (Refereed) Published
Abstract [en]

Osteoclast formation is controlled by stromal cells/osteoblasts expressing macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), crucial for osteoclast progenitor cell proliferation, survival and differentiation, and osteoprotegerin (OPG) that inhibits the interaction between RANKL and its receptor RANK. Recent data have strongly indicated that the nervous system play an important role in bone biology. In the present study, the effects of the neuropeptide vasoactive intestinal peptide (VIP), present in peptidergic skeletal nerve fibers, on the expression of RANKL, OPG, and M-CSF in osteoblasts and stromal cells have been investigated. VIP and pituitary adenylate cyclase-activating polypeptide 38 (PACAP-38), but not secretin, stimulated rankl mRNA expression in mouse calvarial osteoblasts. In contrast, VIP inhibited the mRNA expressions of opg and m-csf, effects shared by PACAP-38, but not by secretin. VIP did not affect rankl, opg or m-csf mRNA expression in mouse bone marrow stromal cells. The effects by VIP on the mRNA expression of rankl, opg and m-csf were all potentiated by the cyclic AMP phosphodiesterase inhibitor rolipram. In addition, VIP robustly enhanced the phosphorylation of ERK and the stimulatory effect by VIP on rankl mRNA was inhibited by the MEK1/2 inhibitor PD98059. These observations demonstrate that activation of VPAC(2) receptors in osteoblasts enhances the RANKL/OPG ratio by mechanisms mediated by cyclic AMP and ERK pathways suggesting an important role for VIP in bone remodelling. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.

Place, publisher, year, edition, pages
Wiley , 2011. Vol. 112, no 12, 3732-3741 p.
Keyword [en]
VIP, Rankl, Osteoblast, Bone
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-47542DOI: 10.1002/jcb.23304PubMedID: 21815197OAI: diva2:442896
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2012-11-12Bibliographically approved

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