Insulin-like Growth Factor I Stimulates Proliferation and Fas-Mediated Apoptosis of Human Osteoblasts

Kawakami, Atsushi; Nakashima, Tomoki; Tsuboi, Masahiko; Urayama, Satoshi; Matsuoka, Naoki; Ida, Hiroaki; Kawabe, Yojiro; Sakai, Hideaki; Migita, Kiyoshi; Aoyagi, Takahiko; Nakashima, Munetoshi; Maeda, Kenji; Eguchi, Katsumi

doi:10.1006/bbrc.1998.8728

Cited by 46 publications

(28 citation statements)

References 17 publications

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“…IGF-I also protects colon cancer cells from death factorinduced apoptosis (Remacle-Bonnet et al 2000). In contrast to the survival-promoting effects of IGF-I reported here, it has been demonstrated that stimulation of human osteoblasts with IGF-I induces expression of Fas and subsequently increases their susceptibility to Fas-mediated apoptosis when co-cultured with FasL + cells (Kawakami et al 1998). It remains to be seen whether IGF-I increases susceptibility to Fas-mediated apoptosis in murine osteoblasts.…”

Section: Discussioncontrasting

confidence: 93%

Autocrine signals promote osteoblast survival in culture

Tumber

Meikle²,

Hill

2000

Journal of Endocrinology

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We have studied the survival requirements of osteoblasts to test the hypothesis that osteoblasts undergo programmed cell death (PCD) or apoptosis unless they are continuously signalled by other cells not to do so. Osteoblasts survived for 6 days in culture at high cell density in the absence of other cell types, serum or exogenous proteins, but they died with the morphological features of apoptosis in these conditions at low cell density. Osteoblast survival was enhanced during the first 2 days of culture by the addition of the sulphydryl compound, cysteine to the culture medium which was converted intracellularly to the antioxidant glutathione. Catalase, an enzyme decomposing hydrogen peroxide, also protected the cells, whereas superoxide dismutase had no effect. Therefore, osteoblasts in culture are sensitive to toxic compounds derived from molecular oxygen, i.e. hydroxyl radicals or hydrogen peroxide spontaneously generated in CMRL medium containing ascorbate and ferrous ions. Conditioned medium from high density cultures prevented osteoblast apoptosis in low density cultures, as long as antioxidants were also present. The enhancing effect of conditioned medium on osteoblast survival was prevented by neutralizing antibodies to insulin-like growth factor-I (IGF-I) and IGF-II but not by antibodies to either platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF). These results suggest that in addition to regulating cell growth and differentiation, IGF-I and IGF-II also function as survival factors for osteoblasts. Our data also indicate that antioxidants are required for osteoblast survival and that they enhance growth factor mediated osteoblast survival.

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Section: Discussioncontrasting

confidence: 93%

Autocrine signals promote osteoblast survival in culture

Tumber

Meikle²,

Hill

2000

Journal of Endocrinology

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“…Indeed, IGF1 has been shown to modulate Fas expression on the cell surface of several cell types. For instance, in osteoblasts IGF1 stimulates Fas expression (Kawakami et al 1998), whereas IGF1 down-regulates the expression of Fas in PHA-activated cord blood T cells (Tu et al 2000). We assessed the effects of IGF1 on Fas expression in neutrophils by flow cytometry.…”

Section: Igf1 Does Not Affect Fas Expression and Caspase-8 Activationmentioning

confidence: 99%

Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway

Himpe

Degaillier²,

Coppens³

et al. 2008

Journal of Endocrinology

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Apoptosis of human neutrophils is a crucial mechanism for the resolution of inflammation. We previously showed that insulinlike growth factor-1 (IGF1) delays spontaneous neutrophil apoptosis without influencing the secretion of cytokines by these cells. In the present study, we further addressed the role of IGF1 in regulating neutrophil survival in the presence of other factors present during inflammation, and the mechanism involved in delaying apoptosis. We show that IGF1 delays neutrophil apoptosis triggered by the agonistic anti-Fas antibody CH11 and that the effect of IGF1 is comparable in magnitude to that of the acknowledged anti-apoptotic cytokines interferon-g (IFNG) and granulocyte-macrophage colony-stimulating factor (GM-CSF; now known as CSF2). Furthermore, IGF1 exerted additional effects on cell survival in the presence of these cytokines. IGF1 did not affect Fas expression or activation by anti-Fas of caspase-8, but inhibited the depolarization of the mitochondrial membrane. Inhibitor studies indicate that the phosphatidylinositol-3 kinase (PI3K) pathway, but not the MEK-ERK pathway, mediates the effects of IGF1. However, in contrast to CSF2, IGF1 did not induce phosphorylation and translocation to the membrane of AKT, the canonical downstream target of PI3K. We therefore speculate that other downstream targets of PI3K are involved in the delay of neutrophil apoptosis by IGF1, possibly through stabilization of the mitochondrial membrane.

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“…IGF-I exerts also a strong influence on cell proliferation and differentiation (59) and is a potent inhibitor of apoptosis in human osteoblasts (33). The action of IGF-I is mainly mediated through the IGF-I receptor (IGF-IR), which is found throughout the uterus (myometrium, epithelium, and stroma), where cells proliferate in response to added IGF-I (63).…”

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confidence: 99%

Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus

Ivanga

Labrie

Calvo

et al. 2007

Physiological Genomics

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Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus. Physiol Genomics 29: 13-23, 2007; doi:10.1152 doi:10. /physiolgenomics.00291.2005 is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/ proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway.17␤-estradiol; 17␤-estradiol modulation; ovariectomized mice; oligonucleotide microarray; protein tyrosine phosphatase IN MAMMALS, THE UTERUS of a mature female undergoes multiple changes during the estrous cycle that reflect modifications of the uterine endometrium in continuous preparation for embryo implantation. Since the majority of cycles are not associated with conception, they often lead to endometrial degeneration and menstrual bleeding. The endometrium thus exhibits a cyclic pattern of growth, regression, disruption, bleeding, and regeneration throughout reproductive life. These changes are mainly under the control of estrogens, progesterone, and androgens. Disregulation of the uterine vasculature has been found to accompany different sex steroid disturbances (28).17␤-Estradiol (E2) is well known to play the key role in mammalian endometrial physiology, since the proliferation of endometrial cells and the extension of spiral vessels that occur during the proliferative phase of the menstrual cycle are controlled by E2 (20, 46). Estrogen is also frequently associated with endometrial cancer, which comprises two subtypes: endometrioid carcinomas (type I) related to estrogen exposure and nonendometrioid carcinomas (type II), which are independent of E2 action (16). Type I cancers ar...

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Insulin-like Growth Factor I Stimulates Proliferation and Fas-Mediated Apoptosis of Human Osteoblasts

Cited by 46 publications

References 17 publications

Autocrine signals promote osteoblast survival in culture

Autocrine signals promote osteoblast survival in culture

Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway

Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus

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