Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss

Ding, Ke; Wang, Zai Zhao; Hamrick, Mark W.; Deng, Zhong; Zhou, Li Juau; Kang, Baolin; Yan, Sheng; She, Jin Xiong; Stern, David M.; Isales, Carlos M.; Mi, Qing Sheng

doi:10.1016/j.bbrc.2005.12.107

Cited by 129 publications

(129 citation statements)

References 26 publications

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“…Over the last decade, evidence has accumulated of ROS participation in bone resorption, with a direct contribution of osteoclasts generating high concentrations of superoxide anion (O2-) and hydrogen peroxide (H2O2) (Muthusami et al, 2005;Bai et al, 2006). However, the mechanisms by which ROS participate in accelerating the destruction of calcified tissue and hence bone resorption have not been fully explained (Muthusami et al, 2005;Ding et al, 2006). Moreover, the effect of ROS on osteoblastic function remains unclear (Ding et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…However, the mechanisms by which ROS participate in accelerating the destruction of calcified tissue and hence bone resorption have not been fully explained (Muthusami et al, 2005;Ding et al, 2006). Moreover, the effect of ROS on osteoblastic function remains unclear (Ding et al, 2006). It has been demonstrated that osteoblasts produce antioxidants such as glutathione peroxidase (GPx) to protect against ROS, but they also produce tumor necrosis factor-a (TNF-a), which is involved in bone resorption (Isomura et al, 2004;Janssens et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, several risk factors for osteoporosis, such as diabetes mellitus (Ding et al, 2006;Léger et al, 2006) and estrogen deficiency (Godsland, 2005;Muthusami et al, 2005) are associated with increased oxidative stress. In diabetes mellitus, persistent hyperglycemia may cause oxidative stress induced by a variety of mechanisms including glucose autoxidation and accelerated glycation reaction, with the formation of glucose-derived advanced glycosylation end products (AGEs), which in turn catalyze lipid peroxidation (Valko et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Persistent hyperglycemia increases polyol pathway flux, as well as ROS generation rates and AGEs formation, leading to increased GSH oxidation (Oyama et al, 2006). Thus, the association between increased oxidative stress and lower antioxidant defense has an important role in the pathogenesis of diabetic osteopenia Ding et al, 2006). Recently, results from our laboratory have demonstrated that supplementation with antioxidants, such as Vitamin E, decreased oxidative stress and markers of lipid peroxidation, and also increased GSH content, representing a prevention and therapeutic effect on bone loss.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

Duarte

Rodrigues

Rezende

et al. 2010

Braz. J. Pharm. Sci.

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The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acidreactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia ≥250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.Uniterms: Oxidative stress. Lipid peroxidation. Diabetes mellitus. Diabetic osteopenia/experimental study.A relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT) e conteúdo de glutationa reduzida (GSH) no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO). Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 -ratas controle (n = 15) e Grupo 2 -ratas diabéticas (n = 15). O diabetes foi induzido pela aloxana e confirmado pela glicemia ≥250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05) nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05) nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05) da separação trabecular do fêmur, associado à diminuição significativa da espessura trabecular (p<0.05) e volume ósseo trabecular reduzido nas ratas diabéticas. Além disso, o teste biomecânico, V.M.G. Duarte, A. de S. Rodrigues, L.A. de Rezende, A.Ma. de O. Ramos, R.M. de Souza, F.P.F. Neto, A. da C. Medeiros 540 medido pela força máxima, e val...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

Duarte

Rodrigues

Rezende

et al. 2010

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

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“…RAGE overexpression by lentiviral transfection has been shown to inhibit osteoblast proliferation through the suppression of the Wnt, PI3K and ERK pathways (36). Studies using RAGE knockout mice have also shown increased bone mass and bone biomechanical strength and a decreased number of osteoclasts in RAGE -/-mice compared with wild-type mice (37). These data indicate that RAGE plays a modulatory role in the development of osteoporosis.…”

Section: Discussionmentioning

confidence: 97%

Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells

Sun

Yang

et al. 2013

International Journal of Molecular Medicine

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Abstract. Advanced oxidation protein products (AOPPs) as a novel marker of oxidative stress, are involved in a variety of diseases, including osteoporosis. Although a number of studies have shown the possible functions of AOPPs in biological processes, little is known about the role of AOPPs in the pathogenesis of osteoporosis. In this study, we aimed to investigate the effect of AOPPs on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (MSCs). MSCs, isolated from bone marrow, were cultured in the absence or presence of AOPPs (50, 100, 200 and 400 mg/ml). MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase (ALP) activity, the mRNA expression of ALP and collagen I and bone nodule formation were detected to assess osteogenic differentiation. Reactive oxygen species (ROS) generation was analyzed with the probe 2' ,7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The expression of receptor of advanced glycation end-products (RAGE) at the mRNA and protein level was detected by real-time PCR and western blot analysis, respectively. Compared with the control group, AOPPs inhibited MSC proliferation in a dose-and timedependent manner. Moreover, AOPPs induced a significant reduction in ALP activity, as well as a decrease in ALP and collagen I mRNA levels in the MSCs; bone nodule formation was also inhibited. Furthermore, AOPPs increased ROS generation in the MSCs, and upregulated the expression of RAGE at the mRNA and protein level. These results suggest that AOPPs inhibit the proliferation and osteogenic differentiation of MSCs, possibly through the AOPPs-RAGE-ROS pathway; this may be an important mechanism in the development of osteoporosis.

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Periodontal disease as a complication of diabetes mellitus

Taylor¹,

Graves²,

Lamster³

2014

Diabetes Mellitus and Oral Health

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Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss

Cited by 129 publications

References 26 publications

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats

Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells

Periodontal disease as a complication of diabetes mellitus

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