Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells

Kim, Sang Wan; Her, Sun Ju; Park, Seong Jae; Kim, Do-Hee; Park, Kyong Soo; Lee, Hong Kyu; Han, Byung Hee; Kim, Min Seon; Shin, Chan Soo; Kim, Seong Yeon

doi:10.1016/j.bone.2005.04.020

Cited by 184 publications

(176 citation statements)

References 46 publications

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“…Previous studies have reported a significant stimulation of osteoblast proliferation and an increased ALP activity in osteoblasts in response to ghrelin (7,17,18). Ghrelin stimulates growth hormone secretion both in vivo and in vitro, and may therefore have a positive effect on bone.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Levels in Patients with Rickets

Şen

Demirol

et al. 2013

ELECTRON J GEN MED

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Section: Discussionmentioning

confidence: 99%

Ghrelin Levels in Patients with Rickets

Şen

Demirol

et al. 2013

ELECTRON J GEN MED

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“…However, this does not exclude the possibility that ghrelin can signal via alternative intracellular pathways, and perhaps other receptors (Papotti et al 2000, Baldanzi et al 2002. In fact, three recent studies demonstrate that ghrelin has proliferative effects in rodent osteoblasts (Fukushima et al 2005, Kim et al 2005, Maccarinelli et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) pathways in the absence of GHS-R1a

Delhanty¹,

Eerden²,

Velde³

et al. 2006

Journal of Endocrinology

141

118

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Recent studies demonstrate widespread expression of ghrelin among tissues and have uncovered its pleiotropic nature. We have examined gene expression of ghrelin and its two receptor splice variants, growth hormone secretagogue receptors (GHS-R) 1a and 1b, in human bone biopsies and in the human pre-osteoblastic SV-HFO cell line during differentiation. Additionally, we examined proliferative effects of ghrelin and unacylated ghrelin (UAG) in differentiating and non-differentiating cells. We detected GHS-R1b mRNA in human bone and osteoblasts but not ghrelin's cognate receptor GHS-R1a, using two different real-time PCR assays and both total RNA and mRNA. In osteoblasts GHS-R1b mRNA expression remained low during the first 14 days of culture, but increased 300% in differentiating cells by day 21. Both human bone biopsies and osteoblasts expressed ghrelin mRNA, and osteoblasts were found to secrete ghrelin.Overall, ghrelin gene expression was greater in differentiating than non-differentiating osteoblasts, but was not increased during culture in either group. Ghrelin and UAG induced thymidine uptake dose-dependently, peaking at 1 and 10 nM respectively, at day 6 of culture in both non-differentiating and differentiating osteoblasts. The proliferative response to ghrelin and UAG declined with culture time and state of differentiation. The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. Overall, our data suggest new roles for ghrelin and UAG in modulating human osteoblast proliferation via a novel signal transduction pathway.

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“…Treatment with GHRP-6 did not increase GFAP levels but stimulated proliferation in the hypothalamus and hippocampus. GHRP-6 and ghrelin stimulate the proliferation of a wide number of cells including osteoblasts (Kim et al 2005), cardiomyocytes (Pettersson et al 2002), somatotrophs (Dieguez & Casanueva 2000), endothelial cells (Rossi et al 2009) and adipocytes (Thompson et al 2004) and may also affect the CNS by protecting neurons from apoptosis (Frago et al 2002, 2011, Delgado-Rubin de Célix et al 2006, Delgado-Rubin et al 2009). We also evaluated the possible effect of GH and GHRP-6 on neuron number and did not observed any changes in the levels of Tuj1 in the hypothalamus or hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Baquedano¹,

Chowen²,

Argente³

et al. 2013

Journal of Endocrinology

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GH and GH secretagogues (GHSs) are involved in many cellular activities such as stimulation of mitosis, proliferation and differentiation. As astrocytes are involved in developmental and protective functions, our aim was to analyse the effects of GH and GH-releasing hexapeptide on astrocyte proliferation and differentiation in the hypothalamus and hippocampus. Treatment of adult male Wistar rats with GH (i.v., 100 mg/day) for 1 week increased the levels of glial fibrillary acidic protein (GFAP) and decreased the levels of vimentin in the hypothalamus and hippocampus. These changes were not accompanied by increased proliferation. By contrast, GH-releasing hexapeptide (i.v., 150 mg/day) did not affect GFAP levels but increased proliferation in the areas studied. To further study the intracellular mechanisms involved in these effects, we treated C6 astrocytoma cells with GH or GH-releasing hexapeptide and the phosphatidylinositol 3 0 -kinase (PI3K) inhibitor, LY294002, and observed that the presence of this inhibitor reverted the increase in GFAP levels induced by GH and the proliferation induced by GH-releasing hexapeptide. We conclude that although GH-releasing hexapeptide is a GHS, it may exert GH-independent effects centrally on astrocytes when administered i.v., although the effects of both substances appear to be mediated by the PI3K/Akt pathway.

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Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells

Cited by 184 publications

References 46 publications

Ghrelin Levels in Patients with Rickets

Ghrelin Levels in Patients with Rickets

Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) pathways in the absence of GHS-R1a

Differential effects of GH and GH-releasing peptide-6 on astrocytes

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