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RANK Ligand (rank + ligand)
Selected AbstractsSerum osteoprotegerin is increased in Crohn's disease: A population-based case control studyINFLAMMATORY BOWEL DISEASES, Issue 4 2005Charles N Bernstein MD Abstract Background: There is a potential interface between osteoporosis and the chronic inflammation of inflammatory bowel disease (IBD), and the osteoprotegerin (OPG)/receptor for activated nuclear factor-,B (RANK)/RANK ligand (RANKL) signaling pathway may be an important mediator, although data are limited. Methods: We conducted a population-based case-control seroassay study to look for alterations in serum OPG and soluble RANKL (sRANKL). The study population included IBD patients who were 18 to 50 years old with Crohn's disease (CD; n = 287) or ulcerative colitis (UC; n = 166), age-matched healthy controls (n = 368), and nonaffected siblings of IBD patients (n = 146). Serum OPG and sRANKL were measured by enzyme-linked immunoassay. Sex-specific reference ranges were derived from the healthy controls. Results: Analysis of variance (ANOVA) confirmed significant group differences in women for mean serum OPG (P = 0.018). CD women had higher values of OPG than UC women (P = 0.028) or healthy controls (P = 0.045), whereas the other groups were similar. OPG levels were above the reference range in 13/173 (8%) of CD women, exceeding the expected proportion (P = 0.032). In contrast, no differences in OPG were seen in men between controls, CD, or UC. Estrogen use in women (P = 0.000002) and corticosteroid use in men (P = 0.026) were associated with higher OPG levels. In multivariate analysis, CD diagnosis (P = 0.031) and estrogen use (P = 0.000002) were independently associated with higher OPG levels. No group differences were seen in mean serum sRANKL measurements. Conclusions: An OPG:sRANKL imbalance with OPG exceeding sRANKL should inhibit osteoclastogenesis and promote bone formation. CD is associated with increased fracture risk, and possibly, the paradoxically higher OPG is a counterregulatory response to factors such as inflammatory cytokines, promoting high bone turnover. Alternatively, elevated OPG in CD may reflect T-cell activation. [source] Osteoclast Inhibitory Peptide 2 Inhibits Osteoclast Formation via Its C-Terminal FragmentJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001Sun Jin Choi Abstract Osteoclast inhibitory peptide 2 (OIP-2) is a novel autocrine/paracrine factor produced by osteoclasts (OCLs) that inhibits bone resorption and OCL formation in vitro and in vivo. It is identical to the asparaginyl endopeptidase legumain. During maturation of OIP-2, a signal peptide and a 17-kDa C-terminal fragment (CTF) are cleaved to produce the mature enzyme. To determine if enzyme activity is required for inhibition of OCL formation or if only the CTF is responsible for these effects, we synthesized His-tagged complementary DNA (cDNA) constructs for the CTF of OIP-2, the proform of OIP-2, and the "mature enzyme" form of OIP-2. The proform or the CTF portion of OIP-2 inhibited OCL formation in a dose-dependent manner in murine bone marrow cultures stimulated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The mature form of OIP-2, which was enzymatically active, did not inhibit OCL formation. In addition, OIP-2 inhibited OCL formation in cultures of highly purified human OCL precursor cells or RAW264.7 cells stimulated with 10 ng/ml of receptor activator of NF-,B (RANK) ligand. Binding studies with His-tagged OIP-2 showed expression of a putative OIP-2 receptor on RAW264.7 cells treated with RANK ligand for 4 days and human marrow cultures treated with 1,25(OH)2D3 for 3 weeks. These data show that the CTF of OIP-2, rather than the mature enzyme, mediates the inhibitory effects of OIP-2 through a putative receptor on OCL precursors. [source] Proposed Standard Nomenclature for New Tumor Necrosis Factor Family Members Involved in the Regulation of Bone Resorption ,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2000Article first published online: 1 DEC 2000 Abstract Recently, three new family members of the tumor necrosis factor (TNF) ligand and receptor signaling system that play a critical role in the regulation of bone resorption have been identified and cloned. These also have been shown to play an important role in regulating the immune system. A proliferation of synonyms for these molecules has led to miscommunication and redundancy. To resolve this, the President of the American Society for Bone and Mineral Research (ASBMR) appointed a special committee to recommend a standard nomenclature. After considerable deliberation and after vetting by workers in the field, the Committee recommends the names of receptor activator of NF-,B (RANK) for the membrane receptor, RANK ligand (RANKL) for the ligand, and osteoprotegerin (OPG) for the decoy receptor. [source] Low-energy laser stimulates tooth movement velocity via expression of RANK and RANKLORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 3 2008S Fujita Structured Abstract Authors,,, Fujita S, Yamaguchi M, Utsunomiya T, Yamamoto H, Kasai K Objective,,, Recent studies have demonstrated that low-energy laser irradiation stimulates bone formation in vitro and in vivo. However, very little is known about the effects of laser irradiation on osteoclastogenesis. The receptor activator of the nuclear factor- kB (RANK),/,RANK ligand (RANKL),/,osteoprotegerin (OPG) system is essential and sufficient for osteoclastogenesis. The present study was designed to examine the effects of low-energy laser irradiation on expressions of RANK, RANKL, and OPG during experimental tooth movement. Design,,, To induce experimental tooth movement in rats, 10 g of orthodontic force was applied to the molars. Next, a Ga,Al,As diode laser was used to irradiate the area around the moved tooth and the amount of tooth movement was measured for 7 days. Immunohistochemical staining with RANK, RANKL, and OPG was performed. Real time PCR was also performed to elucidate the expression of RANK in irradiated rat osteoclast precursor cells in vitro. Results,,, In the irradiation group, the amount of tooth movement was significantly greater than in the non-irradiation group by the end of the experimental period. Cells that showed positive immunoreactions to the primary antibodies of RANKL and RANK were significantly increased in the irradiation group on day 2 and 3, compared with the non-irradiation group. In contrast, the expression of OPG was not changed. Further, RANK expression in osteoclast precursor cells was detected at an early stage (day 2 and 3) in the irradiation group. Conclusion,,, These findings suggest that low-energy laser irradiation stimulates the velocity of tooth movement via induction of RANK and RANKL. [source] Osteoprotegerin in the Inner Ear May Inhibit Bone Remodeling in the Otic Capsule,THE LARYNGOSCOPE, Issue 1 2005Andreas F. Zehnder MD Abstract Objectives: To elucidate factors that may be responsible for the inhibition of remodeling of bone within the otic capsule. Methods: Expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK), and RANK ligand (RANKL) were assayed in samples of bone obtained from the otic capsule, calvarium, and femur, and from the soft tissue within the cochlea using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in mice. Immunostaining was used for histologic localization of the gene products. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the amount of OPG within perilymph, serum, and cerebrospinal fluid. The micro-anatomy of the interface between the otic capsule and the fluid spaces of the cochlea was investigated by brightfield and phase-contrast microscopy and by three-dimensional reconstruction in the mouse and human. Results: OPG, a powerful inhibitor of bone remodeling, was expressed at extremely high levels within the soft tissue of the cochlea and was present in the perilymph at very high concentrations. The OPG produced within the inner ear may diffuse into the surrounding otic capsule, where it may be responsible for inhibition of bone turnover. Our anatomic studies revealed an extensive system of interconnected canaliculi within the otic capsule that had direct openings into the fluid spaces of the inner ear, thus providing a possible anatomic route for the diffusion of OPG from the inner ear into the surrounding bone. Conclusion: OPG, a potent inhibitor of osteoclast formation and function, is expressed at high levels within the inner ear and is secreted into the perilymph and the surrounding bone and may serve to inhibit active bone remodeling within the otic capsule, especially immediately adjacent to the cochlea. By this means, the cochlear soft tissue may control the nature of the surrounding petrous bone. [source] Epistatic Interactions between Genomic Regions Containing the COL1A1 Gene and Genes Regulating Osteoclast Differentiation may Influence Femoral Neck Bone Mineral DensityANNALS OF HUMAN GENETICS, Issue 2 2007Tie-Lin Yang Summary Bone mineral density (BMD) is a primary risk indicator of osteoporotic fractures, which are largely determined by the actions of multiple genes. Genetic linkage studies have seldom explored epistatic interaction of genes for BMD. To evaluate potential genetic interactions for BMD at the femoral neck (FN) we conducted a variance component linkage analysis, to test epistatic effects between the genomic region containing the COL1A1 (collagen type I alpha 1) gene and the genomic regions containing genes regulating osteoclast differentiation (e.g. TNFRSF11A encoding RANK (receptor for activation of nuclear factor kappa B), TNFSF11 encoding RANKL (RANK ligand), IL1A (interleukin-1 alpha), IL6 (interleukin-6), etc) in 3998 Caucasian subjects from 434 pedigrees. We detected significant epistatic interactions between the regions containing COL1A1 with IL6 (p = 0.004) and TNFRSF1B encoding TNFR2 (tumor necrosis factor receptor 2) (p = 0.003), respectively. In summary, we identified the epistatic effects on BMD between regions containing several prominent candidate genes. Our results suggested that the IL6 and TNFRSF1B genes may regulate FN BMD variation through interactions with the COL1A1 gene, which should be substantiated by other, or population-based, association studies. [source] The relationship between circulating osteoprotegerin levels and bone mineral metabolism in healthy womenCLINICAL ENDOCRINOLOGY, Issue 2 2004Ki Won Oh Summary objective, Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. Moreover, OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between circulating OPG levels and female bone status in human populations is unclear. In this study we undertook to investigate the relationship between circulating OPG levels and bone mineral metabolism in healthy women. patients and measurements, Our subjects were 287 women aged 37,73 years (mean age 51·5 years). The serum concentrations of OPG were determined by enzyme-linked immunosorbent assay (ELISA). The biochemical markers of bone turnover and FSH were measured using standard methods. Bone mineral densities at the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. results, Postmenopausal women had a significantly higher mean value of serum OPG than premenopausal women (1358·5 ± 32·5 pg/ml vs. 1228·8 ± 33·3 pg/ml, P < 0·01). Serum OPG levels were positively correlated with age (r = 0·169, P < 0·01), as were urine deoxypyridinoline levels (r = 0·133, P < 0·05) and serum FSH levels (r = 0·187, P < 0·01) in a bivariate correlation analyses. In a multiple regression analysis, only urine calcium excretion was identified as a significant predictor for serum OPG levels. conclusions, Circulating OPG levels were found to be associated with urine calcium excretion and menopause in healthy women. Our observations suggest that circulating OPG levels reflect an antiresorptive activity in bone, and they are related to endogenous oestrogen levels. [source] 2D TR-NOESY Experiments Interrogate and Rank Ligand,Receptor Interactions in Living Human Cancer Cells,ANGEWANDTE CHEMIE, Issue 6 2010Silvia Mari Dr. Wer ist der beste? Verschiedene Ligand-Rezeptor-Wechselwirkungen in humanen Krebszelllinien wurden direkt mithilfe der zweidimensionalen TR-NOE-Spektroskopie untersucht (siehe Bild), um die Spezifität der molekularen Erkennung zu prüfen und ein Affinitäts-Ranking mehrerer Liganden zu erhalten. [source] | ||||||||||