Neuropeptide Y functions as a neuroproliferative factor

Hansel, Donna E.; Eipper, Betty A.; Ronnett, Gabriele V.

doi:10.1038/35073601

Cited by 319 publications

(321 citation statements)

References 26 publications

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“…3A). Furthermore, when examining NPY-induced ERK signaling pathway as reported previously [14,16,19,34], NPY failed to activate activity-related site-specific phosphorylation of ERK (Thr202/Tyr204) in isolated adipocytes while NE stimulated it (Fig. 3B).…”

Section: Resultssupporting

confidence: 75%

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Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

et al. 2012

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Section: Resultssupporting

confidence: 75%

“…NPY has been shown to activate ERK pathway in a variety of cells, possibly leading to cell proliferation of neuronal precursor cells [14,16] and progression of cancer [34]. Moreover, Yang et al…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

et al. 2012

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“…Investigation of olfactory neuronal precursor cells in mice with a targeted deletion of NPY revealed a reduction in neuronal precursor proliferation resulting in fewer olfactory neurons (42) and indicated that NPY is required for the normal proliferation of olfactory neurospheres in vitro. (43) Similarly, NPY has been shown in mice to promote the proliferation of neuronal progenitor cells in the dentate gyrus of the hippocampus (28,44) and also in the subventricular zone.…”

Section: Discussionmentioning

confidence: 99%

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

Lee

Doyle

Sainsbury

et al. 2010

Journal of Bone and Mineral Research

100

135

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The neuropeptide Y (NPY) system has been implicated in the regulation of bone homeostasis and osteoblast activity, but the mechanism behind this is unclear. Here we show that Y1 receptor signaling is directly involved in the differentiation of mesenchymal progenitor cells isolated from bone tissue, as well as the activity of mature osteoblasts. Importantly, the mRNA levels of two key osteogenic transcription factors, runx2 and osterix, as well as the adipogenic transcription factor PPAR-g, were increased in long bones of Y1 À/À mice compared with wild-type mice. In vitro, bone marrow stromal cells (BMSCs) isolated from Y1 À/À mice formed a greater number of mineralized nodules under osteogenic conditions and a greater number of adipocytes under adipogenic conditions than controls. In addition, both the number and size of fibroblast colony-forming units formed in vitro by purified osteoprogenitor cells were increased in the absence of the Y1 receptors, suggestive of enhanced proliferation and osteogenesis. Furthermore, the ability of two specific populations of mesenchymal progenitor cells isolated from bone tissue, an immature mesenchymal stem cell population and a more committed osteoprogenitor cell population, to differentiate into osteoblasts and adipocytes in vitro was enhanced in the absence of Y1 receptor signaling. Finally, Y1 receptor deletion also enhanced the mineral-producing ability of mature osteoblasts, as shown by increased in vitro mineralization by BMSCs isolated from osteoblast-specific Y1 À/À mice. Together these data demonstrate that the NPY system, via the Y1 receptor, directly inhibits the differentiation of mesenchymal progenitor cells as well as the activity of mature osteoblasts, constituting a likely mechanism for the high-bone-mass phenotype evident in Y1 À/À mice. ß

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“…NPY is a neurotransmitter widely expressed through the peripheral and central nervous system, and its actions are mediated through the activation of G-protein coupled receptors, namely Y1, Y2, Y4, Y5 and y6 receptors [9]. Through specific activation of the Y1 receptor, NPY has been shown to play a critical role in a number of centrally-regulated physiological functions, such as energy homeostasis [10], anxiety [11], cardiovascular function [12] and neurogenesis [13]. More recently, NPY has been shown to regulate bone homeostasis via actions in peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

Sousa

Baldock

Enriquez

et al. 2012

Bone

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The neuropeptide Y system has emerged as one of the major neural signalling pathways regulating bone homeostasis. Absence of Y1 receptor signalling from bone forming osteoblasts is responsible for an enhancement on bone mass in mice, suggesting that pharmacological blockade of Y1 receptors may offer a novel anabolic treatment option for improving bone mass. Here we show that oral administration of the selective Y1 receptor antagonist BIBO3304 for 8 weeks dose-dependently increases bone mass in mice. Histomorphometric analysis revealed a significant 1.5-fold increase in cancellous bone volume in the femora of mice treated with BIBO3304. Furthermore, bone microarchitecture was improved, with greater trabecular number and trabecular thickness. This increase in bone mass was associated with a significant increase in bone anabolic activity of osteoblasts and, interestingly, was evident despite a coincident increase in bone resorption, as evidenced by an increase in the number of the osteolytic osteoclasts. Changes were also evident in cortical bone, with a significant increase in periosteal mineral apposition rate. Importantly, no adverse extra-skeletal side effects were observed through Y1 receptor antagonism over the 8-week treatment period, with no effects of even the higher BIBO3304 dose on body weight, adiposity, energy metabolism or circulating corticosterone levels. Taken together, this work describes the first NPY-based anabolic treatment for improving bone mass, and highlights the therapeutic potential of blocking Y1 receptor signalling for the prevention of, or recovery from, degenerative skeletal diseases.

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Neuropeptide Y functions as a neuroproliferative factor

Cited by 319 publications

References 26 publications

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

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