The Inhibitory Effects of Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide on Osteoclast Formation Are Associated with Upregulation of Osteoprotegerin and Downregulation of RANKL and RANK

Mukohyama, Hitoshi; Ransjö, Maria; Taniguchi, Hisashi; Ohyama, Takashi; Lerner, Ulf H.

doi:10.1006/bbrc.2000.2599

Cited by 66 publications

(57 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These differences in osteoclast formation could be observed in cultures established both 6 weeks and 12 months after the spinal cord lesion. The result is compatible with the view that increased osteoclast formation, enhanced bone resorption, and osteoporosis may be due to loss of nerve function, a hypothesis that is supported by observations that both CGRP and VIP can inhibit in vitro osteoclastogenesis (Akopian et al, 2000, Mukohyama et al, 2000a.…”

Section: Clinical Evidence For Neuro-supporting

confidence: 87%

Expression and regulatory role of receptors for vasoactive intestinal peptide in bone cells

Lundberg

Lerner

2002

Microscopy Res & Technique

Self Cite

View full text Add to dashboard Cite

An intense network of nerve fibers can be demonstrated in skeletal tissues, not only in the periosteum but also within cortical bone, growth plate, and bone marrow. This neuro-osteogenic network expresses a restricted number of signalling molecules, including neuropeptides, neurotransmitters, and neurotrophins. Several lines of evidence indicate that receptors for these molecules are present on bone cells and that activation of these receptors leads to changes in bone cell activities. In addition, deletion of signalling molecules has been shown to alter bone metabolism. In the present review, these studies are summarized with a focus on distribution and effects of vasoactive intestinal peptide.

show abstract

Section: Clinical Evidence For Neuro-supporting

confidence: 87%

Expression and regulatory role of receptors for vasoactive intestinal peptide in bone cells

Lundberg

Lerner

2002

Microscopy Res & Technique

Self Cite

View full text Add to dashboard Cite

show abstract

“…2 and 3). This suggests that PACAP acts against multiple myeloma, at least in part, by inhibiting sequelae of these induced cytokines, and possibly also be beneficial for inhibiting the increased osteoclastic bone resorption in myeloma bone disease (41)(42)(43). Therefore, combining TNF-a inhibition with NF-nB blockade may enhance the cytotoxicity of multiple myeloma cells by PACAP.…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells

Cortez

Nakamachi

et al. 2006

Cancer Research

View full text Add to dashboard Cite

Multiple myeloma represents a malignant proliferation of plasma cells in the bone marrow, which often overproduces immunoglobulin light chains. We have shown previously that pituitary adenylate cyclase-activating polypeptide (PACAP) markedly suppresses the release of proinflammatory cytokines from light chain-stimulated human renal proximal tubule epithelial cells and prevents the resulting tubule cell injury. In this study, we have shown that PACAP suppresses the proliferation of human K and L light chain-secreting multiple myeloma-derived cells. The addition of PACAP suppressed light chain-producing myeloma cell-stimulated interleukin 6 (IL-6) secretion by the bone marrow stromal cells (BMSCs). A specific antagonist to either the human PACAP-specific receptor or the vasoactive intestinal peptide receptor attenuated the suppressive effect of PACAP on IL-6 production in the adhesion of human multiple myeloma cells to BMSCs. The secretion of IL-6 by BMSCs was completely inhibited by 10 À9 mol/L PACAP, which also attenuated the phosphorylation of both p42/44 and p38 mitogen-activated protein kinases (MAPK) as well as nuclear factor-KB (NF-KB) activation in response to the adhesion of multiple myeloma cells to BMSCs, whereas the inhibition of p42/44 MAPK signaling attenuated PACAP action. The signaling cascades involved in the inhibitory effect of PACAP on IL-6-mediated paracrine stimulation of light chain-secreting myeloma cell growth was mediated through the suppression of p38 MAPK as well as modulation of activation of transcription factor NF-KB. These findings suggest that PACAP may be a new antitumor agent that directly suppresses light chain-secreting myeloma cell growth and indirectly affects tumor cell growth by modifying the bone marrow milieu of the multiple myeloma. (Cancer Res 2006; 66(17): 8796-803)

show abstract

“…PACAP also exerts an inhibitory effect on thyroid hormone-stimulated osteocalcin synthesis via blockade of the p38 MAPK in osteoblast-like MC3T3-E1 cells (Kanno et al, 2005). Besides its effect on osteoblasts, PACAP inhibits osteoclastogenesis and thus reduces bone resorption (Winding et al, 1997;Mukohyama et al, 2000). This effect can be ascribed, at least in part, to a decreased expression of the receptor activator of nuclear factor-B ligand and its receptor, which play a role in osteoclast formation and activation, as well as an increased expression of the receptor activator of nuclear factor-B ligand decoy receptor osteoprotegerin .…”

Section: Effects Of Pituitary Adenylate Cyclase-activating Polypepmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

View full text Add to dashboard Cite

The Inhibitory Effects of Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide on Osteoclast Formation Are Associated with Upregulation of Osteoprotegerin and Downregulation of RANKL and RANK

Cited by 66 publications

References 25 publications

Expression and regulatory role of receptors for vasoactive intestinal peptide in bone cells

Expression and regulatory role of receptors for vasoactive intestinal peptide in bone cells

Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Contact Info

Product

Resources

About