Oxidative stress modulates osteoblastic differentiation of vascular and bone cells

Mody, Nilam; Parhami, Farhad; Sarafian, Theodore A.; Demer, Linda L.

doi:10.1016/s0891-5849(01)00610-4

Cited by 720 publications

(560 citation statements)

References 50 publications

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“…In bonederived preosteoblasts, oxidized low-density lipoprotein (oxLDL) and other bioactive oxidized lipids inhibit the expression of various markers of osteoblast differentiation [34] . Also OxLDL and oxidative products inhibit osteogenic differentiation of mesenchymal stem cells and preosteoblast in favour of an adipogenic differentiation [36,37] . We found that free cholesterol inhibited bone formation, reduced the activity of SOD and increased the level of MDA, which indicated that the free cholesterol increased the oxidative injury in osteoblasts in vitro.…”

Section: Discussionmentioning

confidence: 99%

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Sheng

Tang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Methods: Female Sprague-Dawley rats were randomly separated into 3 groups: (1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet. Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol (E2), osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells (MC3T3-E1) were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. Results: In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol (12.5-50 μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1, and increased the oxidative injury in MC3T3-E1 cells. Conclusion:The results suggest a close correlation between hypercholesterolaemia and osteoporosis. High cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts.

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Section: Discussionmentioning

confidence: 99%

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Sheng

Tang

et al. 2011

Acta Pharmacol Sin

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“…[19] Mody et al found that hydrogen peroxide and xanthine/xanthine oxidase increased intracellular oxygen radicals and enhanced osteoblastic differentiation of vascular cells, and that this effect was blocked by exogenous antioxidants. [20] Also, advanced glycation end products accelerated calcification in microvascular pericytes. [21] Our study demonstrates that AOPP markedly increases the intracellular oxidative stress of HASMCs at 2 h, and that this effect peaks at 6 h. Vitamin E not only attenuated the intracellular oxidative stress induced by AOPP, but also blocked AOPP-induced OPN expression and calcium deposition.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress has also been shown to cause the smooth muscle cell to dedifferentiate. [19][20][21][22] The present study investigates the role of AOPPs, prepared with human serum albumin (HSA) and hypochloric acid (HOCl), in modulating osteoblast differentiation and calcification of human aortic smooth muscle cells (HASMCs) in vitro. Then, we investigate the role of oxidative stress and the possible signal transduction pathway of AOPPs on HASMCs differentiation and calcification.…”

Section: Introductionmentioning

confidence: 99%

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

et al. 2009

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Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidantmediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-a1 (CBF-a1) and osteopontin (OPN) and significantly decreased SM-a-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.

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“…(4,5) Importantly, regardless of whether from a genetic or a dietary source, lipid oxidation products attenuate osteogenic differentiation in vitro. (6)(7)(8) In mice, hyperlipidemia induces bone loss (9,10) and impairs the anabolic effects (11) of intermittent parathyroid hormone (PTH), a regimen now used for the treatment of osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

Sage

Atti

et al. 2010

Journal of Bone and Mineral Research

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In hyperlipidemia, oxidized lipids accumulate in vascular tissues and trigger atherosclerosis. Such lipids also deposit in bone tissues, where they may promote osteoporosis. We found previously that oxidized lipids attenuate osteogenesis and that parathyroid hormone (PTH) bone anabolism is blunted in hyperlipidemic mice, suggesting that osteoporotic patients with hyperlipidemia may develop resistance to PTH therapy. To determine if oxidized lipids account for this PTH resistance, we blocked lipid oxidation products in hyperlipidemic mice with an ApoA-I mimetic peptide, D-4F, and the bone anabolic response to PTH treatment was assessed. Skeletally immature Ldlr À/À mice were placed on a high-fat diet and treated with D-4F peptide and/or with intermittent PTH(1-34) injections. As expected, D-4F attenuated serum lipid oxidation products and tissue lipid deposition induced by the diet. Importantly, D-4F treatment attenuated the adverse effects of dietary hyperlipidemia on PTH anabolism by restoring micro-computed tomographic parameters of bone quality-cortical mineral content, area, and thickness. D-4F significantly reduced serum markers of bone resorption but not bone formation. PTH and D-4F, together but not separately, also promoted bone anabolism in an alternative model of hyperlipidemia, Apoe À/À mice. In normolipemic mice, D-4F cotreatment did not further enhance the anabolic effects of PTH, indicating that the mechanism is through its effects on lipids. These findings suggest that oxidized lipids mediate hyperlipidemia-induced PTH resistance in bone through modulation of bone resorption. ß

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Oxidative stress modulates osteoblastic differentiation of vascular and bone cells

Cited by 720 publications

References 50 publications

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

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