INEB
INEB
TitleNeuropeptide y expression and function during osteoblast differentiation - Insights from transthyretin knockout mice
Publication TypeJournal Article
2010
AuthorsNunes, AF, Liz, MA, Franquinho, F, Teixeira, L, Sousa, V, Chenu, C, Lamghari, M, Sousa, MM
JournalFEBS JournalFEBS J.
Volume277
Issue1
Pagination263 - 275
Date Published2010///
1742464X (ISSN)
3T3 Cells, alpha amidating enzyme, Amidated neuropeptide, amidation, Amides, animal cell, animal tissue, Animals, article, Base Sequence, Bone Density, bone development, bone marrow cell, Bone Marrow Cells, Bone marrow stromal cells, bone mass, cartilage cell, cell differentiation, Cells, Cultured, Chondrocytes, controlled study, developmental stage, DNA Primers, embryo, embryo development, Homeostasis, immunohistochemistry, male, Mice, Mice, Knockout, mouse, Mus, neuropeptide Y, nonhuman, NPY, ossification, osteoblast, Osteoblastic differentiation, Osteoblasts, osteocyte, Osteocytes, peptide synthesis, prealbumin, priority journal, protein expression, protein function, radioimmunoassay, regulatory mechanism, reverse transcription polymerase chain reaction, RNA, Messenger, stroma cell, Stromal Cells, trabecular bone
To better understand the role of neuropeptide Y (NPY) in bone homeostasis, as its function in the regulation of bone mass is unclear, we assessed its expression in this tissue. By immunohistochemistry, we demonstrated, both at embryonic stages and in the adult, that NPY is synthesized by osteoblasts, osteocytes, and chondrocytes. Moreover, peptidylglycine α-amidating monooxygenase, the enzyme responsible for NPY activation by amidation, was also expressed in these cell types. Using transthyretin (TTR) KO mice as a model of augmented NPY levels, we showed that this strain has increased NPY content in the bone, further validating the expression of this neuropeptide by bone cells. Moreover, the higher amidated neuropeptide levels in TTR KO mice were related to increased bone mineral density and trabecular volume. Additionally, RT-PCR analysis established that NPY is not only expressed in MC3T3-E1 osteoblastic cells and bone marrow stromal cells (BMSCs), but is also detectable by RIA in BMSCs undergoing osteoblastic differentiation. In agreement with our in vivo observations, in vitro, TTR KO BMSCs differentiated in osteoblasts had increased NPY levels and exhibited enhanced competence in undergoing osteoblastic differentiation. In summary, this work contributes to a better understanding of the role of NPY in the regulation of bone formation by showing that this neuropeptide is expressed in bone cells and that increased amidated neuropeptide content is related to increased bone mass. © 2009 FEBS.
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