Disease relevance of Tnfrsf11b

• These data demonstrate that short term Fc-OPG treatment has powerful anti-erosive effects, principally on bone, even though synovitis is not affected [1].
• In humans, prominent T lymphocytes have been identified in periodontal disease, and diseased tissues showed elevated RANKL mRNA expression, as well as decreased OPG mRNA expression [2].
• We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT) [3].
• The receptor activator of nuclear factor-kappaB ligand inhibitor osteoprotegerin is a bone-protective agent in a rat model of chronic renal insufficiency and hyperparathyroidism [3].
• Consequently, regulation of OPG production by the dental follicle likely affects the alveolar bone resorption needed for tooth eruption [4].

High impact information on Tnfrsf11b

• Morphometric analysis revealed that the addition of PTH to PEG sTNFRI or OPG resulted in higher bone volume and higher osteoblast numbers in both AIA and CIA [5].
• Analysis of bone erosion revealed a significant bone-sparing effect of monotherapy with PEG sTNFRI or OPG in both models, whereas IL-1Ra was only effective in CIA [5].
• Osteoprotegerin (a decoy receptor for RANK ligand) did not significantly alter the effects of UDP on NF-kappaB localization or osteoclast survival, consistent with a direct action [6].
• A decoy receptor for RANKL, osteoprotegerin, (OPG) impinges on this system and regulates osteoclast numbers and activity [1].
• After induction of CIA in Dark Agouti rats, test animals were treated with or without Fc-OPG (3 mg/kg/day) subcutaneously for 5 days, beginning at the onset of disease [1].

Chemical compound and disease context of Tnfrsf11b

• In this study we show that the inhibition of bone resorption by treatment with the hormone calcitonin, the cytokine osteoprotegerin, or the drug alendronate, completely inhibits the generation of the fetuin-mineral complex in response to etidronate injection [7].
• Therefore, we conclude that doses of osteoprotegerin that inhibit bone resorption are able to potently inhibit the calcification of arteries that is induced by warfarin treatment and by vitamin D treatment [8].

Biological context of Tnfrsf11b

• Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption [9].
• Previous studies had shown that PKC-alpha gene expression is downregulated at the time (Day 3) that OPG expression is downregulated [4].
• CONCLUSIONS: In the early stages of arthritis, synovial RANKL is closely involved in osteoclastogenesis, and various changes in synovial cytokines, including down-regulation of OPG, probably accelerate osteoclast formation [10].
• To test this hypothesis, we examined the effects of substrate microarchitecture on production of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL), which have been identified as a key regulatory system of bone remodeling [11].
• Expression of mRNA for osteoprotegerin and receptor activator of nuclear factor kappa beta ligand (RANKL) during root resorption induced by the application of heavy orthodontic forces on rat molars [12].

Anatomical context of Tnfrsf11b

• In arthritic joints, Fc-OPG depleted osteoclast numbers by over 75% and diminished bone erosion scores by over 60% [1].
• Detection of osteoprotegerin (OPG) and its ligand (RANKL) mRNA and protein in femur and tibia of the rat [13].
• Nitric oxide donor increases osteoprotegerin production and osteoclastogenesis inhibitory activity in bone marrow stromal cells from ovariectomized rats [14].
• In addition, OPG promoter stably integrated into an osteoblast cell line was activated by phorbol myristate acetate [15].
• OPG is produced by a variety of cells of mesenchymal origin and has been demonstrated to be present in osteoblasts and osteocytes [15].

Associations of Tnfrsf11b with chemical compounds

• Immunohistochemical observation also showed that 2,2'-(hydroxynitrosohydrazino)bis-ethanamine increased OPG expression of osteochondral cells located at metaphyseal endosteum and calcified cartilage of proximal femurs in ovariectomized rats [14].
• We further show that phorbol myristate acetate, an activator of protein kinase C, activated the secretion of OPG [15].
• MATERIALS AND METHODS: Osteogenic differentiation was induced in hMSCs cultured in maintenance medium (MM) by addition of ascorbate, beta-glycerophosphate, and dexamethasone (ODM) and was assessed by measuring alkaline phosphatase activity, expression of osteopontin, osteoprotegerin, RANKL, and mineralization [16].
• The ORX-induced increase in urinary deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried plum coinciding with down-regulation of gene expression for receptor activator of NFkappa-B ligand (RANKL) and osteoprotegerin (OPG) in the bone [17].
• Changes in receptor activator of nuclear factor-kappaB, and its ligand, osteoprotegerin, bone-type alkaline phosphatase, and tartrate-resistant acid phosphatase in ovariectomized rats [18].

Regulatory relationships of Tnfrsf11b

• Injection of phorbolmyristate acetate (PMA), an activator of protein kinase C (PKC) that in turn upregulates OPG expression, also delayed eruption by 1 day [4].

Other interactions of Tnfrsf11b

• The co-expression of OPG and RANKL in the same bone cell types confirms their strictly coupled action in the regulation of bone metabolism [13].
• In the bone marrow, RT-PCR did not clearly detect the expression of IL-6, RANKL or OPG mRNA [10].
• RESULTS: When given acutely, both E(2) and the CR extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1alpha1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur [19].

Analytical, diagnostic and therapeutic context of Tnfrsf11b

• Osteoclasts were identified using TRAP staining and expression of the mRNA for OPG and RANKL was identified by in situ hybridization [1].
• Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis [1].
• The present study had the main aim of showing the localization of OPG and RANKL mRNA and protein in serial sections of the rat femurs and tibiae by immunohistochemistry (IHC) and in situ hybridization (ISH) [13].
• In this study, using reverse transcription polymerase chain reaction techniques to examine OPG gene expression showed that PMA injection increased OPG gene expression in the dental follicle at Day 3 as compared to the controls [4].
• By Northern and Western blot analysis, osteoprotegerin mRNA and protein levels were very low in endothelial cells plated on the non-integrin cell attachment factor, poly-d-lysine [20].

References