Oxidized low density lipoprotein enhanced RANKL expression in human osteoblast-like cells. Involvement of ERK, NFkappaB and NFAT

Mazière, Cécile; Salle, V.; Gomila, Cathy; Mazière, Jean‐Claude

doi:10.1016/j.bbadis.2013.05.033

Cited by 38 publications

(37 citation statements)

References 36 publications

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“…The HFD must therefore have negated the impact of these pro-osteoclastogenic signals specifically within the microenvironment of trabecular bone. In vitro studies have given conflicting results as oxLDL inhibits RANKL-induced differentiation of the RAW 264.6 pre-osteoclastic cell line (41), but increased basal levels of pro-osteoclastogenic RANKL in MG-63 human osteosarcoma cells (40). However, it is possible that the HFD-induced decrease in the expression of Wnt5a is responsible for the decrease in trabecular osteoclasts since this Wnt ligand promotes osteoclastogenesis in trabecular but not cortical bone (37).…”

Section: Discussionmentioning

confidence: 99%

Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice

Liu

Almeida

Weinstein

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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ApoE-null (ApoE-KO) mice fed a high-fat diet (HFD) develop atherosclerosis, due in part to activation of vascular inflammation by oxidized low-density lipoprotein. Since bone loss also occurs in these mice, we used them to investigate the impact of oxidized lipids on bone homeostasis and to search for underlying pathogenic pathways. Four-month-old female ApoE-KO mice fed a HFD for three months exhibited increased levels of oxidized lipids in bone, as well as decreased femoral and vertebral trabecular and cortical bone mass, compared with ApoE-KO mice on normal diet. Despite HFD-induced increase in expression of Alox15, a lipoxygenase that oxidizes LDL and promotes atherogenesis, global deletion of this gene failed to ameliorate the skeletal impact of HFD. Osteoblast number and function were dramatically reduced in trabecular and cortical bone of HFD-fed mice, whereas osteoclast number was modestly reduced only in trabecular bone, indicating that an imbalance in favor of osteoclasts was responsible for HFD-induced bone loss. These changes were associated with decreased osteoblast progenitors and increased monocyte/macrophages in the bone marrow as well as increased expression of IL-1␤, IL-6, and TNF. HFD also attenuated Wnt signaling as evidenced by reduced expression of Wnt target genes, and it decreased expression of pro-osteoblastogenic Wnt ligands. These results suggest that oxidized lipids decrease bone mass by increasing anti-osteoblastogenic inflammatory cytokines and decreasing pro-osteoblastogenic Wnt ligands.

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Section: Discussionmentioning

confidence: 99%

Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice

Liu

Almeida

Weinstein

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…[27] It has been proposed that oxidized LDL increase Receptor activator of nuclear factor kappa-B ligand expression on osteoblast and increase interaction with osteoclast which affect bone remodeling and may cause decrease in BMD. [32] Further, in animal models, the primary cholesterol metabolite, 27-hydroxycholesterol, interacts with estrogen and liver X-receptors, decreases osteoblast differentiation, and increases osteoclastogenesis, thereby resulting in increased bone resorption and decrease in BMD. [33] BMD at femoral neck showed positive correlation with TG, which was lost when adjusted for various factors including age and BMI.…”

Section: Discussionmentioning

confidence: 99%

Relationship of lipid parameters with bone mineral density in Indian population

Garg

Marwaha

Tandon

et al. 2014

Indian J Endocr Metab

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Introduction:Cardiovascular disease and osteoporosis share common risk factors including dyslipidemia. There are conflicting reports of differential relation of various lipid parameters on bone mineral density (BMD). Hence, we studied the correlation between lipid parameters and BMD in healthy adult.Materials and Methods:A total of 2347 participants (male 39.4%; female 60.6%) included in this cross-sectional study were divided according to sex and age. Fasting blood samples were drawn for biochemical parameters. BMD at lumbar spine, femur, and forearm were measured by dual energy X-ray absorptiometry (DXA).Results:In males, BMD at femur and lumbar spine decreased significantly with increasing quartiles of total cholesterol (TC) (P < 0.0001, and 0.004) and low-density lipoprotein cholesterol (LDL-c) (P = 0.001, and 0.01). In premenopausal women, BMD at femoral neck (P = 0.001) and lumbar spine (P = 0.029) showed declining trend with LDL-c (P = 0.007). In postmenopausal women, only BMD at total femur decreased significantly with TC (P = 0.024) and LDL-c (P = 0.036). All above findings were confirmed in correlation studies. In multiple regression analysis after adjusting for age, body mass index, ionized calcium, alkaline phosphatase, 25 hydroxy vitamin D, and parathyroid hormone levels correlation of BMD with TC and LDL-c persisted. TC, LDL-c was higher in subjects with low bone density compared those with normal bone density in both sexes.Conclusions:TC and LDL-c had weak but significant negative correlation with BMD at femur and lumbar spine.

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“…The NF-κB, MAPK, ERK, and NFAT signaling pathways have been demonstrated to regulate RANKL expression in osteoblast cells [29,41] and VSMCs [11,28]. In this study, exenatide inhibited the activation of NF-κB in human CVSMCs.…”

Section: Discussionmentioning

confidence: 64%

Exenatide can inhibit calcification of human VSMCs through the NF-kappaB/RANKL signaling pathway

Zhan

Tan

Wang

et al. 2014

Cardiovasc Diabetol

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BackgroundArterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined.MethodsCalcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-κB ligand (RANKL) was silenced by small interference RNA (siRNA).ResultsExenatide, an agonist of GLP-1 receptor, attenuated β-glycerol phosphate (β-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-κB) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor α1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-κB and increased p-AMPKα levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-κB (p-Ser276, p-Ser536) level was observed in cells treated with exenatide or exenatide + BAY11-7082.ConclusionGLP-1RA exenatide can inhibit human VSMCs calcification through NF-κB/RANKL signaling.

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Oxidized low density lipoprotein enhanced RANKL expression in human osteoblast-like cells. Involvement of ERK, NFkappaB and NFAT

Abstract: This work describes a new molecular mechanism and elucidates the signaling pathway whereby oxidized low density lipoprotein, by means of its lipid moiety, can modulate the crosstalk between osteoblasts/osteoclasts and bone remodeling, leading to an eventual risk of osteoporosis.

Cited by 38 publications

References 36 publications

Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice

Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice

Relationship of lipid parameters with bone mineral density in Indian population

Exenatide can inhibit calcification of human VSMCs through the NF-kappaB/RANKL signaling pathway

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