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
Idioma:
Português
Tipo (Avaliação Docente):
Científica
Contacto:
lamghari@ineb.up.pt