The Influence of Prenatal Fumonisin Exposure on Bone Properties, as well as OPG and RANKL Expression and Immunolocalization, in Newborn Offspring Is Sex and Dose Dependent

The current study examined the effects of exposure of pregnant dams to fumonisins (FBs; FB1 and FB2), from the seventh day of pregnancy to parturition, on offspring bone metabolism and properties. The rats were randomly divided into three groups intoxicated with FBs at either 0, 60, or 90 mg/kg b.w. Body weight and bone length were affected by fumonisin exposure, irrespective of sex or dose, while the negative and harmful effects of maternal FBs’ exposure on bone mechanical resistance were sex and dose dependent. The immunolocalization of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL), in bone and articular cartilage, indicated that the observed bone effects resulted from the FB-induced alterations in bone metabolism, which were confirmed by the changes observed in the Western blot expression of OPG and RANKL. It was concluded that the negative effects of prenatal FB exposure on the general growth and morphometry of the offspring bones, as a result of the altered expression of proteins responsible for bone metabolism, were dose and sex dependent.

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α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

Journal of Endocrinology ◽

10.1677/joe.1.05995 ◽

2005 ◽

Vol 185 (3) ◽

pp. 401-413 ◽

Cited By ~ 18

Author(s):

Jung-Min Koh ◽

Young-Sun Lee ◽

Chang-Hyun Byun ◽

Eun-Ju Chang ◽

Hyunsoo Kim ◽

...

Keyword(s):

Bone Marrow ◽

Lipoic Acid ◽

Nuclear Factor Κb ◽

Human Bone ◽

Human Bone Marrow ◽

Mouse Bone Marrow ◽

Dependent Manner ◽

Nuclear Factor ◽

Receptor Activator ◽

Dose Dependent

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although α-lipoic acid (α-LA) has been shown to act as a thiol antioxidant, its effect on bone cells has not been determined. Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of α-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor κB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that α-LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned medium (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin (OPG) secretion. Despite increasing the RANKL/OPG ratio, α-LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts and in a mouse bone marrow cell culture system, and reduced bone resorption in a dose-dependent manner. In addition, α-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by α-LA without any posttranslational processing. In contrast, α-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that α-LA suppresses osteoclastogenesis by directly inhibiting RANKL–RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that α-LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

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Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone Properties in Glucocorticoid-Induced Osteoporosis

Microscopy and Microanalysis ◽

10.1017/s1431927617012363 ◽

2017 ◽

Vol 23 (5) ◽

pp. 989-1001 ◽

Cited By ~ 7

Author(s):

Priscila L. Sequetto ◽

Reggiani V. Gonçalves ◽

Aloísio S. Pinto ◽

Maria G. A. Oliveira ◽

Izabel R. S. C. Maldonado ◽

...

Keyword(s):

Tissue Repair ◽

Protein Composition ◽

Serum Levels ◽

Mechanical Resistance ◽

Protein Levels ◽

Bone Properties ◽

Calcium Phosphorus ◽

Mechanical Remodeling ◽

Dose Dependent ◽

Dose Dependent Effect

AbstractBy using an experimental model of dexamethasone-induced osteoporosis we investigated the effects of different therapeutic schemes combining sodium alendronate (SA) and simvastatin on bone mineral and protein composition, microstructural and mechanical remodeling. Wistar rats were randomized into eight groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg, respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea, especially in non-treated animals, which showed severe osteoporosis. Dexamethasone also induced bone microstructural fragility and reduced mechanical resistance, which were associated with a marked depletion in mineral mass, collagenous and non-collagenous protein levels in cortical and cancellous bone. Although SA has attenuated osteoporosis severity, the effectiveness of drug therapy was enhanced combining alendronate and simvastatin. The restoration in serum parameters, organic and inorganic bone mass, and mechanical behavior showed a dose-dependent effect that was potentially related to the complementary mechanisms by which each drug acts to induce bone anabolism, accelerating tissue repair.

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Methylation Status of a Single CpG Locus 3 Bases Upstream of TATA-Box of Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Gene Promoter Modulates Cell- and Tissue-Specific RANKL Expression and Osteoclastogenesis

Molecular Endocrinology ◽

10.1210/me.2006-0205 ◽

2007 ◽

Vol 21 (1) ◽

pp. 148-158 ◽

Cited By ~ 45

Author(s):

Riko Kitazawa ◽

Sohei Kitazawa

Keyword(s):

Methylation Status ◽

Gene Promoter ◽

Nuclear Factor Κb ◽

Tata Box ◽

Nuclear Factor ◽

Rankl Expression ◽

Tissue Specific ◽

Receptor Activator

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Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2011-200198 ◽

2011 ◽

Vol 71 (1) ◽

pp. 108-113 ◽

Cited By ~ 41

Author(s):

Maria J H Boumans ◽

Rogier M Thurlings ◽

Lorraine Yeo ◽

Dagmar Scheel-Toellner ◽

Koen Vos ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Joint Destruction ◽

Bone Destruction ◽

Nuclear Factor Κb ◽

Type I ◽

Nuclear Factor ◽

Rankl Expression ◽

Osteoclast Precursors ◽

Receptor Activator ◽

Hands And Feet

ObjectivesTo examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients.MethodsTwenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp–van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor κB ligand (RANKL), osteocalcin and cross-linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment.ResultsAfter 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor κB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p<0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change.ConclusionsRituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA.

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Bone metabolism and the receptor activator of nuclear factor-κB ligand (RANKL) pathway: a comprehensive review

Orthopaedics and Trauma ◽

10.1016/j.mporth.2021.07.006 ◽

2021 ◽

Vol 35 (5) ◽

pp. 297-304

Author(s):

Christopher Peake ◽

Kanishk Shah ◽

Matthew C. Solan

Keyword(s):

Bone Metabolism ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Comprehensive Review ◽

Receptor Activator

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Skeletal changes in osteoprotegerin and receptor activator of nuclear factor-κb ligand mRNA levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism

Bone ◽

10.1016/j.bone.2004.03.012 ◽

2004 ◽

Vol 35 (1) ◽

pp. 256-265 ◽

Cited By ~ 26

Author(s):

L.S Stilgren ◽

E Rettmer ◽

E.F Eriksen ◽

L Hegedüs ◽

H Beck-Nielsen ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Bone Metabolism ◽

Nuclear Factor Κb ◽

Mrna Levels ◽

Nuclear Factor ◽

Skeletal Changes ◽

Receptor Activator

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Role of Prostaglandin E in Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Osteoblasts Induced by Cell Adhesion to Bone Marrow B-lymphocytes

JOURNAL OF HEALTH SCIENCE ◽

10.1248/jhs.55.832 ◽

2009 ◽

Vol 55 (5) ◽

pp. 832-837 ◽

Cited By ~ 1

Author(s):

Michiko Hirata ◽

Suguru Harada ◽

Chiho Matsumoto ◽

Morichika Takita ◽

Chisato Miyaura ◽

...

Keyword(s):

Bone Marrow ◽

Cell Adhesion ◽

B Lymphocytes ◽

Nuclear Factor Κb ◽

Prostaglandin E ◽

Nuclear Factor ◽

Rankl Expression ◽

Receptor Activator

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Modulatory Effect of 1,25-Dihydroxyvitamin D3on IL1β-Induced RANKL, OPG, TNFα, and IL-6 Expression in Human Rheumatoid Synoviocyte MH7A

Clinical and Developmental Immunology ◽

10.1155/2013/160123 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 35

Author(s):

Xiaoke Feng ◽

Chengyin Lv ◽

Fang Wang ◽

Ke Gan ◽

Miaojia Zhang ◽

...

Keyword(s):

Biological Function ◽

Bone Erosion ◽

Osteoclast Formation ◽

Nuclear Factor ◽

Rankl Expression ◽

Potent Inducer ◽

Receptor Activator ◽

Inflammatory Milieu ◽

Vitamin D Supplement ◽

Inflammatory Action

Receptor activator of nuclear factorκB ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis. Considering that 1,25(OH)2D3has been suggested as a potent inducer of RANKL expression, it should clarify whether vitamin D supplement could result in RANKL overexpression and thereby facilitate excessive osteoclastogenesis and bone resorption in RA. Here, we investigated modulatory effect of 1,25(OH)2D3on the expression of RANKL and its decoy receptor osteoprotegerin (OPG) in an inflammatory condition of human rheumatoid synoviocyte MH7A. MH7A cells were stimulated with IL1βand then treated with different concentrations of 1,25(OH)2D3for 48 h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNFβmRNA expression in cells and IL-6 protein in supernatants were observed in IL1β-induced MH7A in the presence of 1,25(OH)2D3compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both 1,25(OH)2D3and IL1β. In summary, although it has a biological function to induce RANKL expression, 1,25(OH)2D3could upregulate OPG/RANKL ratio and mediate anti-inflammatory action in an inflammatory milieu of synoviocyte, contributing to the inhibition of inflammation-induced osteoclastogenesis in RA.

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