| Title | NPY revealed as a critical modulator of osteoblast function in vitro: New insights into the role of Y1 and Y2 receptors |
| Publication Type | Journal Article |
| 2009 |
| Authors | Teixeira, L, Sousa, DM, Nunes, AF, Sousa, MM, Herzog, H, Lamghari, M |
| Journal | Journal of Cellular BiochemistryJ. Cell. Biochem. |
| Volume | 107 |
| Issue | 5 |
| Pagination | 908 - 916 |
| Date Published | 2009/// |
| 07302312 (ISSN) |
| alkaline phosphatase, animal cell, animal tissue, Animals, article, Bone, Bone Marrow Cells, bone remodeling, Calcium, cell activity, cell differentiation, cell function, Cell Line, cell stimulation, controlled study, down regulation, extracellular matrix, gene expression regulation, genetic transcription, Homeostasis, immunoglobulin enhancer binding protein, in vitro study, Mice, neuropeptide Y, neuropeptide Y1 receptor, neuropeptide Y2 receptor, nonhuman, NPY, nuclear factor Y, osteoblast, Osteoblasts, osteoclast differentiation factor, Osteoprotegerin, phenotype, priority journal, promoter region, protein expression, RANK Ligand, Receptors, Neuropeptide Y, Reverse Transcriptase Polymerase Chain Reaction, signal transduction, stem cell, Stromal Cells, upregulation, Y1 receptor, Y2 receptor |
| Neuropeptide Y (NPY) has recently emerged as a potential regulator of bone homeostasis. However, the relevance of NPY's role in osteoblast activity and the biological functions involving NPY receptors in bone homeostasis remain to be clarified. Here we report that chronically elevated NPY levels leaded to a modulation of the level of Y2 receptor expression marked with a transient down and upregulation according to the stage of osteoblast differentiation. We also show that NPY is a negative regulator of Y1 receptor expression. The pharmalogical activation of Y2 receptor with its agonist resulted in similar effect. Functional analysis also revealed the osteogenic potential of NPY with osteoblast phenotype markers being significantly enhanced in osteoprogenitor cells stimulated by NPY, probably due to the down-regulation of Y1 receptor. In contrasts, these cells exhibit a reduction in calcium deposition in extracellular matrix most likely mediated via Y2 receptor signalling. Furthermore, we show that NPY modulates receptor activator of nuclear factor kB (NF-kB) (RANK) ligand and osteoprotegerin, two key factors regulating bone remodelling. Specifically, NPY inhibits the transcriptional activity of RANKL promoter in osteoprogenitor cells and enhances OPG expression in osteoblasts at early stages of differentiation. However, NPY effect on OPG seemed to be unrelated to Y2 receptor activation. Taken together the present data supported the contribution of NPY pathway in bone homeostasis via a direct action on osteoblasts cells. © 2009 Wiley-Liss, Inc. |
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