Neuropeptide Y expression and function during osteoblast differentiation – insights from transthyretin knockout mice

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Meriem Lamghari (Author) Other

Journal

Title: FEBS Journal

Pages: 1-13

ISSN: 1742-464X

Publisher: Wiley-Blackwell

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): 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 a-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. Abbreviations ALP, alkaline phosphatase; BMD, bone mineral density; BMSC, bone marrow stromal cell; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HPRT, hypoxanthine-guanine phosphoribosyltransferase; KO, knockout; microCT, micro computed tomography; NF200, neurofilament 200; NPY, neuropeptide Y; PAM, peptidylglycine a-amidating monooxygenase; PGP9.5, protein gene product 9.5; RANK, receptor activator of nuclear factor-jB; T4, thyroxine; TTR, transthyretin. FEBS Journal (2009) ª 2009 The Authors Journal compilation ª 2009 FEBS 1

Abstract (EN): 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 a-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. Abbreviations ALP, alkaline phosphatase; BMD, bone mineral density; BMSC, bone marrow stromal cell; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HPRT, hypoxanthine-guanine phosphoribosyltransferase; KO, knockout; microCT, micro computed tomography; NF200, neurofilament 200; NPY, neuropeptide Y; PAM, peptidylglycine a-amidating monooxygenase; PGP9.5, protein gene product 9.5; RANK, receptor activator of nuclear factor-jB; T4, thyroxine; TTR, transthyretin. FEBS Journal (2009) ª 2009 The Authors Journal compilation ª 2009 FEBS 1

Language: Portuguese

Type (Professor's evaluation): Scientific