Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation

Dai, Zixun; Li, Y.; Quarles, L. Darryl; Song, Tao; Pan, Wei; Zhou, Hong‐Hao; Xiao, Zhousheng

doi:10.1016/j.phymed.2007.04.003

Cited by 202 publications

(196 citation statements)

References 32 publications

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“…Furthermore, the inhibition of growth resulting from RES treatment in these cells is in line with a number of studies that find RES to exert an anti-proliferative effect [48][49][50][51]. However, it should be noted that there are at least two reports in the literature showing a stimulatory effect of RES on the proliferation of osteoblasts in vitro at concentrations of RES comparable to the ones used here [52,53]. Therefore, it is possible that the anti-proliferative potential of RES depends on the type of cell that is being studied.…”

Section: Discussionsupporting

confidence: 87%

In Vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs

Billack¹,

Radkar²,

Adiabouah³

2008

Cellular and Molecular Biology Letters

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Resveratrol (RES), a component of red wine, possesses antiinflammatory properties. The studies described in the present work were aimed at evaluating the potential for RES and related stilbene analogs (piceatannol, PIC; pterostilbene, TPS; trans-stilbene, TS; and trans-stilbene oxide, TSO) to exhibit toxicity towards RAW 264.7 mouse macrophages. The effect of TS, TSO, RES and TPS on RAW 264.7 macrophage viability was determined by two standard methods: (a) the MTT assay and (b) the trypan blue dye exclusion test. Whereas macrophages were more sensitive to PIC (LC 50 trypan ~ 1.3 μM) and to TPS (LC 50 trypan ~ 4.0 μM and LC 50 MTT ~ 8.3 μM) than to RES (LC 50 trypan ~ 8.9 μM and LC 50 MTT ~ 29.0 μM), they were relatively resistant to TSO (LC 50 trypan ~ 61.0 μM and LC 50 MTT > 100 μM) and to TS (LC 50 trypan ≥ 5.0 μM and LC 50 MTT ≥ 5.0 μM). The ability of selected stilbenes (RES, TPS and PIC) to exhibit growth inhibitory effects was also examined. Although RES and TPS were observed to inhibit cell proliferation in macrophages (IC 50 ≤ 25 µM), these cells were resistant to growth inhibition by PIC (IC 50 ≥ 50 µM). The data obtained in the present analysis demonstrate that substituted stilbene compounds such as RES have the capacity to exhibit cytotoxic and anti-proliferative activities in macrophages.

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Section: Discussionsupporting

confidence: 87%

In Vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs

Billack¹,

Radkar²,

Adiabouah³

2008

Cellular and Molecular Biology Letters

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“…Addition of oestrogen receptor antagonist and ERK1/2 pathway inhibitors but not p38 MAPK pathway blockers attenuated resveratrol-induced gene expression (71) . Icariin, a flavonol glycoside isolated from herbs, was present in rat plasma after oral administration of Gushudan extract (72) .…”

Section: Effect Of Polyphenols On Transcription Factorsmentioning

confidence: 92%

When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

2009

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Recent research has provided insights into dietary components that may optimise bone health and stimulate bone formation. Fruit and vegetable intake, as well as grains and other plant-derived food, have been linked to decreased risk of major chronic diseases including osteoporosis. This effect has been partially attributed to the polyphenols found in these foods. Thus, it has been suggested that these compounds may provide desirable bone health benefits through an action on bone cell metabolism. The present review will focus on how some polyphenols can modulate osteoblast function and reports which cellular signalling pathways are potentially implicated. However, to date, despite numerous investigations, few studies have provided clear evidence that phenolic compounds can act on osteoblasts. Polyphenols cited in the present review seem to be able to modulate the expression of transcription factors such as runt-related transcription factor-2 (Runx2) and Osterix, NF-κB and activator protein-1 (AP-1). It appears that polyphenols may act on cellular signalling such as mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP), oestrogen receptor and osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) and thus may affect osteoblast functions. However, it is also important to take in account the possible interaction of these compounds on osteoclast metabolism to better understand the positive correlation reported between the consumption of fruit and vegetables and bone mass.

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“…This effect is associated with a rapid activation of ERK1 and ERK2, and also can be inhibited by the ERK inhibitor PD98059. Resveratrol enhances osteoblastic maturation and calcium deposition into the extracellular matrix (53) and its effects on osteoblastic differentiation are mediated through NO/cGMP pathway (54). Sex hormone involvement in MSC function also includes leptin-and vitamin D-linked increases in aromatase activity during osteogenesis, leading to osteogenic differentiation of MSCs (55) and significant E2 linked increases in the lipid stores of differentiated adipocytes (52).…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Sex Steroids and Stem Cell Function

Ray

Novotny

Crisostomo

et al. 2008

Mol Med

102

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Gender dimorphisms exist in the pathogenesis of a variety of cardiovascular, cardiopulmonary, neurodegenerative, and endocrine disorders. Estrogens exert immense influence on myocardial remodeling following ischemic insult, partially through paracrine growth hormone production by bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells. Estrogens also facilitate the mobilization of endothelial progenitor cells to the ischemic myocardium and enhance neovascularization at the ischemic border zone. Moreover, estrogens limit pathological myocardial remodeling through the inhibitory effects on the proliferation of the cardiac fibroblasts. Androgens also may stimulate endothelial progenitor cell migration from the bone marrow, yet the larger role of androgens in disease pathogenesis is not well characterized. The beneficial effects of sex steroids include alteration of lipid metabolism in preadipocytes, modulation of bone metabolism and skeletal maturation, and prevention of osteoporosis through their effects on osteogenic precursors. In an example of sex steroid-specific effects, neural stem cells exhibit enhanced proliferation in response to estrogens, whereas androgens mediate inhibitory effects on their proliferation. Although stem cells can offer significant therapeutic benefits in various cardiovascular, neurodegenerative, endocrine disorders, and disorders of bone metabolism, a greater understanding of sex hormones on diverse stem cell populations is required to improve their ultimate clinical efficacy. In this review, we focus on the effects of estrogen and testosterone on various stem and progenitor cell types, and their relevant intracellular mechanisms.

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Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation

Cited by 202 publications

References 32 publications

In Vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs

In Vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs

When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

Sex Steroids and Stem Cell Function

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