Oxidized LDL binding to LOX-1 enhances MCP-1 expression in cultured human articular chondrocytes

Akagi, Masao; Ueda, Atsuko; Teramura, Takeshi; Kanata, S.; Sawamura, Tatsuya; Hamanishi, Chiaki

doi:10.1016/j.joca.2008.06.019

Cited by 25 publications

(17 citation statements)

References 26 publications

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“…Although IL-8 is found to induce chondrocyte hypertrophy [29], it also induces endothelial permeability by transactivating the VEGF receptor-2 [30]. Enhanced expression of MCP-1 is observed in cultured human articular chondrocytes in response to oxidized low-density lipoprotein and may be involved in cartilage degeneration [31].Immunosuppression by MCP-1 has also been observed [32]. However, the role of MCP-1 during bone formation requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Enhanced the Angiogenic Capability of Human Chondrocytes by Regulating Gi/NF-kB-Dependent Angiogenic Factor Expression

et al. 2014

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Lysophosphatidic acid (LPA) has been found to mediate myeloid differentiation, stimulate osteogenesis, alter cell proliferation and migration, and inhibit apoptosis in chondrocytes. The effect of LPA on the angiogenic capability of chondrocytes is not clear. This study aimed to investigate its effect on the angiogenic capability of human chondrocytes and the underlying mechanism of these effects. Human chondrocyte cell line, CHON-001, commercialized human chondrocytes (HC) derived from normal human articular cartilage, and human vascular endothelial cells (HUVECs) were used as cell models in this study. The angiogenic capability of chondrocytes was determined by capillary tube formation, monolayer permeability, cell migration, and cell proliferation. An angiogenesis protein array kit was used to evaluate the secretion of angiogenic factors in conditioned medium. Angiogenin, insulin-like growth factor-binding protein 1 (IGFBP-1), interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) mRNA and protein expressions were evaluated by Q-RT-PCR and EIA, respectively. LPA receptor (LPAR) expression was determined by RT-PCR. Signaling pathways were clarified using inhibitors, Western blot analysis, and reporter assays. The LPA treatment promoted the angiogenic capability of CHON-001 cells and HC, resulting in enhanced HUVEC capillary tube formation, monolayer permeability, migration, and cell growth. Angiogenin, IGFBP-1, IL-8, MCP-1, MMP-9, and VEGF mRNA and protein expressions were significantly enhanced in LPA-treated chondrocytes. LPA2, 3, 4 and 6 were expressed in CHON-001 and HC cells. Pretreatment with the Gi/o type G protein inhibitor, pertussis toxin (PTX), and the NF-kB inhibitor, PDTC, significantly inhibited LPA-induced angiogenin, IGFBP-1, IL-8, MCP-1, MMP-9, and VEGF expressions in chondrocytes. The PTX pretreatment also inhibited LPA-mediated NF-kB activation, suggesting the presence of active Gi/NF-kB signaling in CHON-001 and HC cells. The effect of LPA on the angiogenesis-inducing capacity of chondrocytes may be due to the increased angiogenesis factor expression via the Gi/NF-kB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Enhanced the Angiogenic Capability of Human Chondrocytes by Regulating Gi/NF-kB-Dependent Angiogenic Factor Expression

et al. 2014

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“…In vivo, the antibody suppressed arterial lipid accumulation [48], neointimal hyperplasia in response to arterial injury [122], CRP-induced vascular hyperpermeability [96], neutrophil invasion after lipopolysaccharide challenge in rats [90] and myocardial ischemia-reperfusion injury [51]. Human monoclonal antibody for human LOX-1 has also been developed using Xenomouse and it inhibits oxLDL-induced ROS formation, RhoA/Rac1 activation and MCP-1 expression [19, 89, 153], suggesting that antibody therapy is feasible. LOX-1 inhibition with small-molecule compounds (drug-like compound) is more useful in terms of oral availability and medical costs but may be challenging since LOX-1 seems somewhat different from “druggable” targets such as G protein-coupled receptors, channels, enzymes and proteases [154].…”

Section: Therapeutic Potential Of Lox-1 Inhibition For Cardiovascularmentioning

confidence: 99%

The Discovery of LOX-1, its Ligands and Clinical Significance

Yoshimoto

Fujita

Kakino

et al. 2011

Cardiovasc Drugs Ther

137

104

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LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL), a key molecule in the pathogenesis of atherosclerosis.The basal expression of LOX-1 is low but highly induced under the influence of proinflammatory and prooxidative stimuli in vascular endothelial cells, smooth muscle cells, macrophages, platelets and cardiomyocytes. Multiple lines of in vitro and in vivo studies have provided compelling evidence that LOX-1 promotes endothelial dysfunction and atherogenesis induced by oxLDL. The roles of LOX-1 in the development of atherosclerosis, however, are not simple as it had been considered. Evidence has been accumulating that LOX-1 recognizes not only oxLDL but other atherogenic lipoproteins, platelets, leukocytes and CRP. As results, LOX-1 not only mediates endothelial dysfunction but contributes to atherosclerotic plaque formation, thrombogenesis, leukocyte infiltration and myocardial infarction, which determine mortality and morbidity from atherosclerosis. Moreover, our recent epidemiological study has highlighted the involvement of LOX-1 in human cardiovascular diseases. Further understandings of LOX-1 and its ligands as well as its versatile functions will direct us to ways to find novel diagnostic and therapeutic approaches to cardiovascular disease.

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“…LOX-1 is expressed on the main cells involved in atherogenesis as well as on the plaques themselves. 56 Although LOX-1 is located on a number of non-vascular cells such as chondrocytes and intestinal cells, 15,57 it is not as widely expressed as other scavenger receptors such as Cluster of Differentiation 36 (CD36). It is therefore an attractive target for the development of selective drug delivery systems.…”

Section: Lox-1 As a Target For The Selective Delivery Of Drugsmentioning

confidence: 99%

The role of lectin-like oxidised low-density lipoprotein receptor-1 in vascular pathology

Shaw

Seese

Ponnambalam

et al. 2014

Diabetes and Vascular Disease Research

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The lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) is a vascular scavenger receptor that plays a central role in the pathogenesis of atherothrombotic disease, which remains the main cause of mortality in the Western population. Recent evidence indicates that targeting LOX-1 represents a credible strategy for the management vascular disease and the current review explores the role of this molecule in the diagnosis and treatment of atherosclerosis. LOX-1-mediated pro-atherogenic effects can be inhibited by anti-LOX-1 monoclonal antibodies and procyanidins, whereas downregulation of LOX-1 expression has been achieved by antisense oligonucleotides and a specific pyrrole-imidazole polyamide. Furthermore, LOX-1 can be utilised for plaque imaging using monoclonal antibodies and even the selective delivery of anti-atherosclerotic agents employing immunoliposome techniques. Also, plasma levels of the circulating soluble form of LOX-1 levels are elevated in atherosclerosis and therefore may constitute an additional diagnostic biomarker of vascular pathology.

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Oxidized LDL binding to LOX-1 enhances MCP-1 expression in cultured human articular chondrocytes

Abstract: Our results suggest that ox-LDL enhances MCP-1 expression in HACs and supports the hypothesis that ox-LDL is involved in cartilage degeneration.

Cited by 25 publications

References 26 publications

Lysophosphatidic Acid Enhanced the Angiogenic Capability of Human Chondrocytes by Regulating Gi/NF-kB-Dependent Angiogenic Factor Expression

Lysophosphatidic Acid Enhanced the Angiogenic Capability of Human Chondrocytes by Regulating Gi/NF-kB-Dependent Angiogenic Factor Expression

The Discovery of LOX-1, its Ligands and Clinical Significance

The role of lectin-like oxidised low-density lipoprotein receptor-1 in vascular pathology

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