Cell death in cultured human Saos2 osteoblasts exposed to low‐density lipoprotein

Klein, Benjamin Y.; Rojansky, Nathan; Ben‐Yehuda, Arie; Abou-Atta, I.; Abedat, Suzan; Friedman, G.

doi:10.1002/jcb.10603

Cited by 27 publications

(27 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of TRIM63 overexpression is consistent with previous reports on the global effects of glucocorticoids on human bone marrow stromal cells and SaOS2 cells [7,[10][11]. According to the previous report, glucocorticoids suppressed the proliferation and promoted osteoblastic differentiation.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells

et al. 2010

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 91%

“…In SaOS2 cells, stimulation with glucocorticoids suppresses growth and promotes activity of alkaline phosphatase, a differentiation marker of the osteoblasts [10,11]. In this study, we performed a comprehensive mi-NheI and ClaI, and ligated into pTRE2puro vector.…”

mentioning

confidence: 99%

Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells

et al. 2010

View full text Add to dashboard Cite

“…Although lipid oxidation has been noted in other tissues with advancing age (30), our findings are the first to document an age-related increase in lipoxygenase expression and lipid oxidation in the murine skeleton. That lipid oxidation has negative effects on osteoblasts was previously suggested by in vitro evidence that oxidized low density lipoprotein stimulates apoptosis of osteoblastic cells (73,74) and that oxidized palmitoylarachidonyl-phosphatidylcholine inhibits BMP-2-induced osteoblast differentiation (75). The ROS/FoxO/PPAR␥/␤-catenin cascade elucidated here is most likely responsible for such anti-osteogenic effects because BMP-2-induced osteoblastogenesis depends on Wnt signaling (76).…”

Section: Discussionmentioning

confidence: 51%

Increased Lipid Oxidation Causes Oxidative Stress, Increased Peroxisome Proliferator-activated Receptor-γ Expression, and Diminished Pro-osteogenic Wnt Signaling in the Skeleton

Almeida

Ambrogini

Han

et al. 2009

Journal of Biological Chemistry

237

189

View full text Add to dashboard Cite

Loss of bone mass with advancing age in mice is because of decreased osteoblast number and is associated with increased oxidative stress and decreased canonical Wnt signaling. However, the underlying mechanisms are poorly understood. We report an age-related increase in the lipid oxidation product 4-hydroxynonenal (4-HNE) as well as increased expression of lipoxygenase and peroxisome proliferator-activated receptor-␥ (PPAR␥) in the murine skeleton. These changes together with decreased Wnt signaling are reproduced in 4-month-old mice bearing a high expressing allele of the lipoxygenase Alox15. The addition of 4-HNE to cultured osteoblastic cells increases oxidative stress, which in turn diverts ␤-catenin from T-cell-specific transcription factors to Forkhead box O (FoxO) transcription factors, thereby attenuating the suppressive effect of ␤-catenin on PPAR␥ gene expression. Oxidized lipids, acting as ligands of PPAR␥, promote binding of PPAR␥2 to ␤-catenin and reduce the levels of the latter, and they attenuate Wnt3a-stimulated proliferation and osteoblast differentiation. Furthermore, oxidized lipids and 4-HNE stimulate apoptosis of osteoblastic cells. In view of the role of oxidized lipids in atherogenesis, the adverse effects of lipoxygenase-mediated lipid oxidation on the differentiation and survival of osteoblasts may provide a mechanistic explanation for the link between atherosclerosis and osteoporosis.Age-related bone loss is primarily because of an insufficient number of osteoblasts (1, 2) attributed to exhaustion of multipotential mesenchymal stem cell progenitors (3, 4) and the diversion of these progenitors toward the adipocyte lineage (5-11). Increased osteoblast apoptosis may also be involved as we recently demonstrated that loss of bone mass and strength in C57BL/6 (B6) 3 mice with advancing age is associated with an increase in the prevalence of apoptotic osteoblasts and a corresponding decrease in osteoblast number and bone formation rate (12). Moreover, these changes are accompanied by increased oxidative stress and diminished canonical Wnt signaling, a critical regulator of bone formation. Wnts are secreted proteins that bind to a Frizzled receptor and a low density lipoprotein receptor-related protein 5 (LRP5) or LRP6 co-receptor, resulting in a rise in the level of ␤-catenin by preventing its degradation by the proteasome. Binding of ␤-catenin to members of TCF family converts them from repressors to activators of a variety of genes, including those involved in the differentiation and survival of osteoblasts (13-16). Importantly, however, ␤-catenin is also an essential partner of the FoxO family of transcription factors, which defend against oxidative stress by stimulating the transcription of oxidant scavenging enzymes such as manganese superoxide dismutase and catalase (17). In fact, we have elucidated that oxidative stress compromises ␤-catenin/TCF-mediated transcription and osteoblastogenesis because of competition between FoxO and TCF for a limited pool of ␤-catenin (18). Such competiti...

show abstract

“…Accordingly, we (6) and others (20,29) have reported that oxLDL particles induce the apoptosis of osteoblastic cells followed by annexin V staining, DNA fragmentation, loss of lysosomal integrity, and appearance of pro-apoptotic proteins. Furthermore, increasing concentrations of oxysterols such as 7␤-hydroxycholesterol and 7-ketocholesterol resulted in the reduction of MG-63 cell viability (from 20 -30 M) as indicated by the loss of MTT activity after 48 h of incubation.…”

Section: Determination Of Hormesis-like Effects Induced By Oxldl and mentioning

confidence: 77%

Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells

Hamel¹,

Abed²,

Brissette³

et al. 2008

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Hamel P, Abed E, Brissette L, Moreau R. Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells. Am J Physiol Cell Physiol 294: C1021-C1033, 2008. First published February 20, 2008 doi:10.1152/ajpcell.00361.2007.-Epidemiological studies indicate that patients suffering from atherosclerosis are predisposed to develop osteoporosis. Atherogenic determinants such as oxidized low-density lipoprotein (oxLDL) particles have been shown both to stimulate the proliferation and promote apoptosis of bone-forming osteoblasts. Given such opposite responses, we characterized the oxLDL-induced hormesis-like effects in osteoblasts. Biphasic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reductive activity responses were induced by oxLDL where low concentrations (10 -50 g/ml) increased and high concentrations (from 150 g/ml) reduced the MTT activity. Cell proliferation stimulation by oxLDL partially accounted for the increased MTT activity. No alteration of mitochondria mass was noticed, whereas low concentrations of oxLDL induced mitochondria hyperpolarization and increased the cellular levels of reactive oxygen species (ROS). The oxLDL-induced MTT activity was not related to intracellular ROS levels. OxLDL increased NAD(P)H-associated cellular fluorescence and flavoenzyme inhibitor diphenyleneiodonium reduced basal and oxLDL-induced MTT activity, suggesting an enhancement of NAD(P)H-dependent cellular reduction potential. Low concentrations of oxLDL reduced cellular thiol content and increased metallothionein expression, suggesting the induction of compensatory mechanisms for the maintenance of cell redox state. These concentrations of oxLDL reduced osteoblast alkaline phosphatase activity and cell migration. Our results indicate that oxLDL particles cause hormesis-like response with the stimulation of both proliferation and cellular NAD(P)H-dependent reduction potential by low concentrations, whereas high concentrations lead to reduction of MTT activity associated with the cell death. Given the effects of low concentrations of oxLDL on osteoblast functions, oxLDL may contribute to the impairment of bone remodeling equilibrium.osteoblasts; atherosclerosis; oxysterol ELEVATED LEVELS of serum low-density lipoprotein (LDL) particles are considered as the most important atherogenic risk factor. LDL particles are thought to become atherogenic after undergoing oxidative modifications, and key roles of oxidized LDL (various oxidized species collectively designated oxLDL) in atherosclerosis have been largely reviewed by Steinberg (46). OxLDL and oxysterols have been shown to increase or decrease proliferation and trigger the apoptosis process depending on the cell types related to vasculature alterations, nature of oxLDL and oxysterols, and on the concentrations used (52), thus supporting numerous deleterious effects that sustain the development of atherosclerosis. Also, a number of clinical studies suggest an association between cardiovascular disease and the develo...

show abstract

Cell death in cultured human Saos2 osteoblasts exposed to low‐density lipoprotein

Cited by 27 publications

References 54 publications

Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells

Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells

Increased Lipid Oxidation Causes Oxidative Stress, Increased Peroxisome Proliferator-activated Receptor-γ Expression, and Diminished Pro-osteogenic Wnt Signaling in the Skeleton

Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells

Contact Info

Product

Resources

About