RANKL/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects

2013 ◽  
Vol 40 (5) ◽  
pp. 684-694 ◽  
Author(s):  
Addolorata Corrado ◽  
Anna Neve ◽  
Antonio Macchiarola ◽  
Annamaria Gaudio ◽  
Arcangela Marucci ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Population ◽  
Vitamin D3 ◽  
Wnt Pathway ◽  
Nuclear Factor Κb ◽  
Protein Factor ◽  
Osteoblast Activity ◽  
Receptor Activator ◽  
Bone Changes ◽  
Dickkopf 1

Objective.To evaluate the expression of Dickkopf-1 protein factor (DKK-1), DKK-2, and β-catenin, components of the Wnt pathway, in human osteoarthritic (OA) and osteoporotic (OP) osteoblasts and to correlate it to cell metabolic activity, proliferation, and receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) expression.Methods.Primary human osteoblast cultures were obtained from healthy, OA, and OP donors. In each cell population we evaluated DKK-1, DKK-2, nonphosphorylated β-catenin and RANKL/OPG expression, osteocalcin and alkaline phosphatase (ALP) synthesis, and cell proliferation, both in basal condition and after vitamin D3 stimulation.Results.DKK-1 and DKK-2 showed opposite patterns of expression in OA and OP osteoblasts. The RANKL/OPG ratio was significantly higher in the OP group because of a greater expression of RANKL, whereas it was significantly lower in the OA group because of a higher expression of OPG. Treatment with vitamin D3 increased the RANKL/OPG ratio and DKK-2 expression and reduced DKK-1 expression in each cell population, but did not affect β-catenin levels. Both osteocalcin and ALP production and cell proliferation were enhanced in OA cells and reduced in the OP ones.Conclusion.These data confirm that OA and OP are characterized by opposite bone changes, consisting of reduced bone remodeling processes with increased osteoblast activity in OA, and enhanced bone resorptive activity with reduction of osteoblast metabolism in OP, and suggest that the Wnt pathway is involved in the pathogenesis of both diseases.

scholarly journals Effect of tumor necrosis factor inhibition on spinal inflammation and spinal ankylosis in SKG mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Doo-Ho Lim ◽  
Eun-Ju Lee ◽  
Oh Chan Kwon ◽  
Seokchan Hong ◽  
Chang-Keun Lee ◽  
...  
Keyword(s):  
Tnf Inhibitor ◽  
Peripheral Arthritis ◽  
Osteoblast Activity ◽  
Positron Emission ◽  
Tumor Necrosis Factor Inhibition ◽  
Receptor Activator ◽  
Dickkopf 1 ◽  
Necrosis Factor ◽  
Inhibitor Treatment ◽  
Spinal Inflammation

AbstractTo prevent spinal progression in ankylosing spondylitis, initiating TNF-inhibitor treatment as early as possible is suggested. However, the outcomes are inconsistent in previous clinical studies. Here, we investigated the effect of TNF inhibition alone on spinal progression when used during arthritis development in a murine model. We injected 8-week-old SKG mice with curdlan (curdlan group). We injected adalimumab at 3 and 9 weeks after the first curdlan injection (ADA group). The clinical scores of peripheral arthritis decreased in the ADA group at 3 weeks after first adalimumab injection. Using positron emission tomography–magnetic resonance imaging and histologic examination, spinal inflammation was observed in the curdlan group, and was significantly deceased in the ADA group. However, spinal osteoblast activities by imaging using OsteoSense 680 EX and bone metabolism-related cytokines such as receptor activator of nuclear factor-kappa B ligand, osteoprotegerin, Dickkopf-1, and sclerostin levels except IL-17A level were not different between the two groups. We conclude that treating TNF inhibitor alone reduced peripheral arthritis score and spinal inflammation in curdlan-injected SKG mice but did not decrease the spinal osteoblast activity, suggesting little effect on spinal ankylosis.

scholarly journals Alteration of Dickkopf-1 and receptor activator of nuclear factor-κB ligand during PBSC mobilization in healthy donors by G-CSF

2011 ◽  
Vol 47 (8) ◽  
pp. 1143-1144 ◽  
Author(s):  
M Tanaka ◽  
T Yujiri ◽  
Y Tanaka ◽  
N Mitani ◽  
A Tanimura ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Healthy Donors ◽  
Receptor Activator ◽  
Dickkopf 1 ◽  
Pbsc Mobilization

scholarly journals Compounds Isolated from Wikstroemia taiwanensisRegulate Bone Remodeling by Modulating Osteoblast and Osteoclast Activities

2021 ◽  
Vol 12 ◽  
Author(s):  
Zuha Imtiyaz ◽  
Yi-Tzu Lin ◽  
Fang-Yu Liang ◽  
Wen-Fei Chiou ◽  
Mei-Hsien Lee
Keyword(s):  
Bone Remodeling ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Treatment Of Osteoporosis ◽  
Human Osteoblasts ◽  
Osteoblast Activity ◽  
Mineral Deposition ◽  
Receptor Activator ◽  
Primary Human Osteoblasts

Bone remodeling, a dynamic process in which bone formation by osteoblast is preceded by bone resorption by osteoclast, is a vital physiological process for maintaining bone mass and strength, imbalances in which could precipitate osteoporosis. Due to the unilateral mechanism of the existing bone remodeling drugs, identifying compounds that could regulate the balance between osteoclast and osteoblast could improve the treatment of osteoporosis. Here, we show that compounds isolated from Wikstroemia taiwanensis modulate osteoclast and osteoblast activities. Specifically, astragalin (1) and kaempferol 3-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (2), besides increasing mineral deposition, increased alkaline phosphatase activity (137.2% for 1 and 115.8% for 2) and ESR-α expression (112.8% for 1 and 122.5% for 2) in primary human osteoblasts. In contrast, compounds 1, 2, 3, and 5 inhibited tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand-induced osteoclasts by 40.8, 17.1, 25.9, and 14.5% and also decreased the number of TRAP-positive cells by 51.6, 26.8, 20.5, and 18.6%, respectively. Our findings, therefore, showed that compounds isolated from W. taiwanensis could increase osteoblast activity while simultaneously decreasing osteoclast activity, and hence, warrant further evaluation for development as anti-osteoporosis agents.

Opg, Rank, and Rankl in Tooth Development: Co-ordination of Odontogenesis and Osteogenesis

2004 ◽  
Vol 83 (3) ◽  
pp. 241-244 ◽  
Author(s):  
A. Ohazama ◽  
J.-M. Courtney ◽  
P.T. Sharpe
Keyword(s):  
Tooth Development ◽  
Nuclear Factor Κb ◽  
Cellular Interactions ◽  
Rankl Expression ◽  
Dental Papilla ◽  
Spatiotemporal Expression ◽  
Receptor Activator ◽  
Explant Cultures ◽  
Enamel Epithelium ◽  
Tooth Germs

Osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. We analyzed expression of these three genes during murine odontogenesis from epithelial thickening to cytodifferentiation stages. Opg showed expression in the thickening and bud epithelium. Expression of Opg and Rank was observed in both the internal and the external enamel epithelium as well as in the dental papilla mesenchyme. Although Rankl expression was not detected in tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germs. All three genes were detected in developing dentary bone at P0. The addition of exogenous OPG to explant cultures of tooth primordia produced a delay in tooth development that resulted in reduced mineralization. We propose that the spatiotemporal expression of these molecules in early tooth and bone primordia cells has a role in co-ordinating bone and tooth development.

scholarly journals Receptor activator of nuclear factor-κB ligand and osteoprotegerin

Cancer ◽  
2001 ◽  
Vol 92 (3) ◽  
pp. 460-470 ◽  
Author(s):  
Lorenz C. Hofbauer ◽  
Andreas Neubauer ◽  
Armin E. Heufelder
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator

scholarly journals Porphyromonas gingivalis Infection-Associated Periodontal Bone Resorption Is Dependent on Receptor Activator of NF-κB Ligand

2013 ◽  
Vol 81 (5) ◽  
pp. 1502-1509 ◽  
Author(s):  
Xiaozhe Han ◽  
Xiaoping Lin ◽  
Xiaoqian Yu ◽  
Jiang Lin ◽  
Toshihisa Kawai ◽  
...  
Keyword(s):  
B Cells ◽  
Bone Resorption ◽  
Fusion Protein ◽  
Porphyromonas Gingivalis ◽  
Nuclear Factor Κb ◽  
Infected Group ◽  
T And B Cells ◽  
Content Type ◽  
Receptor Activator ◽  
Control Fusion

ABSTRACTPorphyromonas gingivalisis one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) inP. gingivalisinfection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 × 109P. gingivalisbacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition toP. gingivalisinfection. Robust serum IgG and salivary IgA antibody (P< 0.01) and T cell proliferation (P< 0.05) responses toP. gingivaliswere detected at day 7 and peaked at day 28 inP. gingivalis-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (P< 0.01) and periodontal bone resorption (P< 0.05) were significantly elevated at day 28 in theP. gingivalis-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in theP. gingivalis-infected group compared to the levels in the uninfected group (P< 0.01). Injection of anti-RANKL antibody (P< 0.05) or OPG-Fc (P< 0.01), but not L6-Fc, into rat gingival papillae afterP. gingivalisinfection resulted in significantly reduced periodontal bone resorption. This study suggests thatP. gingivalisinfection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells.

Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor κB ligand/osteoprotegerin ratio

Bone ◽  
2008 ◽  
Vol 42 (3) ◽  
pp. 535-546 ◽  
Author(s):  
Dutmanee Seriwatanachai ◽  
Kanogwun Thongchote ◽  
Narattaphol Charoenphandhu ◽  
Jantarima Pandaranandaka ◽  
Kukiat Tudpor ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator
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