Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen temporal bones were examined from 11 patients who had metastatic temporal bone disease from a distant primary. The salient clinical features were: the high incidence of occult temporal bone involvement (7 of the 10 clinically documented cases), the considerable incidence of melanoma (3 of 10) and the variable correlation between clinical findings and pathologic localization of tumor in the temporal bone. Pathologic examination revealed two distinct modes of tumor spread within the temporal bone: 1) vascularosseous (petrous apex, mastoid, middle ear, external canal); and 2) perineural (nerves in IAC branches, labyrinthine endorgans). Every case was involved by one or both or these routes and no case of CSF-borne metastasis to the perilymphatic space was seen. The external canal was involved extensively in spite of an intact tympanic membrane. Since the presence of symptomatic or occult metastases in the temporal bone affects treatment and prognosis, they must be actively sought by the clinician.
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PMID:Metastatic tumors in the temporal bone--a pathophysiologic study. 37 58

The dialysis encephalopathy syndrome has a geographical distribution related to the aluminium content of the dialysis water supply. There is a close relationship between concentrations of water aluminium and serum aluminium, and patients with dialysis encephalopathy have serum aluminium concentrations greater than 400 microgram/litre. High serum aluminium is also associated with osteomalacic bone disease, and worsening anaemia. In dialysis encephalopathy, elevated concentrations of aluminium are found in CSF and in grey matter, and an aluminium burden of 2-8 g is calculated from whole body in vivo analysis. There is sufficient evidence for an aluminium toxicity syndrome to warrant specific removal of aluminium by water purification systems.
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PMID:Aluminium studies in dialysis encephalopathy. 74 Jun 62

Bone involvement in idiopathic calcium nephrolithiasis is characterized by the following abnormalities: a) the bone density is decreased, the severity of bone loss being dependent upon the existence of hypercalciuria and upon the pathophysiology of this latter: it is inconsistent in the absence of hypercalciuria or when hypercalciuria is of the absorptive type I or II, whereas it is almost constant in fasting hypercalciuria without secondary hyperparathyroidism and constant and severe in the rare true renal hypercalciuria. b) The bone histology (which has been evaluated only in idiopathic hypercalciuric patients) mainly shows a defect in bone formation at the exception of the rare renal hypercalciuria. Osteoclastic hyperresorption is only seen in this latter type of hypercalciuria whereas in the other types of hypercalciuria only an increase of the total or inactive resorption surface is observed. This phenomenon is possibly explained only by a delayed refilling of the resorption lacunae secondary to the decreased bone formation. The osteoid thickness is either normal or decreased despite decrease in mineralization apposition rate which seems therefore to be secondary to the decreased bone formation. c) Symptomatic bone disease in hypercalciuric stone formers is exceptional and always related to a severe long term calcium restriction. d) The biochemical markers of bone resorption tend to be increased in idiopathic hypercalciuria. Hydroxyprolinuria is more often elevated than pyridinolinuria. However pyridinolinuria is negatively correlated to bone density. The contrast between the increase of these bone resorption markers and the usual normality of plasma PTH and of the osteoclastic resorptive surfaces, suggest the role of meat induced acid load which may favor inactive resorption by dissolution of bone buffers. A disturbed profile synthesis of cytokines which induce differentiation and proliferation of the osteoclasts and which modulate the osteoblastic proliferation and function (IL-1, IL-6, TNF-alpha, GM-CSF...) may play a role in the bone loss of calcium stone formers but further studies are necessary to precise its transient or permanent involvement in their bone disease. e) The decrease of bone formation may be explained by the suppressed PTH secretion which may be explained by hypercalcitriolemia. This excess of calcitriol synthesis may be secondary either to monocyte increased synthesis of IL-1 which stimulates the renal 1 alpha-hydroxylase by the mean of an increased PGE2 synthesis or to the relative hypophosphatemia of the calcium stone formers comparatively to healthy controls. Hypercalcitriolemia may originate from the activated monocyte itself. The decrease in bone formation may also be secondary to the action of monokines on the osteoblast differentiation and/or function.
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PMID:[Bone involvement in idiopathic calcium lithiasis]. 756 25

Malignant osteopetrosis is a fatal congenital bone disorder characterized by defective osteoclastic function. Death frequently occurs within the first decade of life. The precise molecular defect(s) that causes osteopetrosis is not known. The possibility that osteoclasts, like macrophages, are controlled by interactions with cytokines suggests that these agents may provide a means of increasing osteoclastic function. Macrophage-colony stimulating factor (M-CSF), a cytokine known to enhance macrophage and osteoclast generation, and recombinant human interferon-gamma (rIFN), a cytokine known to stimulate superoxide generation by white cells, were administered to microphthalmic (mi/mi) mice in an attempt to improve the osteopetrotic condition. Each cytokine was administered separately and in combination to neonatal mi/mi mice for 7 consecutive d. Bone turnover, osteoclast numbers, superoxide generation by white cells, and hematocrit were assessed. rIFN, M-CSF, and a combination of the cytokines stimulates oxygen-derived free radical production by white cells and increased bone resorption. rIFN resulted in a reduction in the number of osteoclasts. This reduction in number was ameliorated by M-CSF. M-CSF alone and in combination with rIFN resulted in improved hematopoietic function, increased weight gain, and increased physical activity of the affected mutants.
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PMID:Combination macrophage-colony stimulating factor and interferon-gamma administration ameliorates the osteopetrotic condition in microphthalmic (mi/mi) mice. 847 20

Congenital osteopetrosis in mammals is an inherited bone disease caused by aberrations in osteoclast development and/or function. Colony-stimulating factor-1 (CSF-1) promotes formation of osteoclasts and is produced by osteoblasts. Recently, two osteopetrotic mutations (op mouse and tl rat) have been shown to have reductions in CSF-1 activity, and CSF-1 injections improve the skeletal manifestations in each. Several different CSF-1 transcripts have been described in mouse and human soft tissues, and differential expression of CSF-1 transcripts has been documented. Thus, we compared gene expression for CSF-1 as reflected by mRNA levels in the bones of tl rats and op mice, and also two other osteopetrotic rat mutations (ia and op). In op mouse calvaria the 4.6 kb transcript was reduced while the 2.3 kb transcript was absent. However, no differences were detected in the levels of these transcripts in mutant and normal calvaria of tl stock. In contrast, CSF-1 transcript levels were elevated in op rat mutants and variable in ia mutants compared to normal littermates. Osteoblast cultures derived from neonatal animals of tl and op rat stock showed the same differences seen in calvarial bone in vivo. The mRNA expression of another growth factor, TGF-beta 1, paralleled that of CSF-1 in vivo and in vitro in the rat mutations. These data demonstrate the emerging molecular heterogeneity among osteopetrotic mutations and underscore the need to evaluate the contributions of these and other cytokines to osteoclast differentiation and function in each mutation.
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PMID:Heterogeneity of colony stimulating factor-1 gene expression in the skeleton of four osteopetrotic mutations in rats and mice. 859 94

Periodontitis is an inflammatory bone disease caused by Gram-negative anaerobic bacteria, but the precise mechanism of bone destruction remains unknown. Activated T lymphocytes secrete receptor activator of NF-kappaB ligand (RANKL) and support the differentiation of monocytes into mature osteoclasts. The purpose of this study was to examine the expression of RANKL and its inhibitor, osteoprotegerin (OPG), in inflamed gingival tissue and to clarify the role of human gingival fibroblasts (HGFs) in osteoclastogenesis regulated by RANKL. HGFs and gingival mononuclear cells (GMCs) were obtained from chronic periodontitis patients during routine periodontal surgery. Expression of OPG and RANKL mRNA in gingival tissue and HGFs was examined with RT-PCR. OPG production was measured using ELISA. Expression of RANKL, CD4, CD8 and CD69 on GMCs was determined by flow-cytometry using RANK-Fc fusion protein and the respective monoclonal antibodies. Osteoclastogenesis by RANKL was assayed by counting the number of tartarate-resistant acid phosphatase (TRAP)-positive cells after culturing human peripheral blood monocytes with recombinant human RANKL and macrophage-colony stimulating factor (M-CSF) for 10 days. OPG and RANKL mRNA were expressed in 80% (16/20) and 25% (5/20) of periodontitis lesions, respectively. OPG, but not RANKL, mRNA was expressed within HGFs. OPG mRNA expression and production by HGFs was augmented by LPS stimulation. All GMC samples expressed CD69, and two of five GMC samples expressed RANKL. The culture supernatant of LPS-stimulated gingival fibroblasts significantly reduced the number of TRAP positive cells generated by culturing monocytes with RANKL and M-CSF. The present study suggests that LPS-stimulated HGFs inhibit monocyte differentiation into osteoclasts through the production of OPG.
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PMID:LPS-stimulated human gingival fibroblasts inhibit the differentiation of monocytes into osteoclasts through the production of osteoprotegerin. 1239 Mar 25

Multiple myeloma has recently been found to induce considerable imbalance in the newly identified system of osteoprotegerin (OPG), receptor activator of nuclear factor KB ligand (RANKL) and RANK. The binding of RANKL to RANK on the surface of osteoclastic precursors in the presence of m-CSF activates the signalling pathways for differentiation and proliferation of an osteoclastic line. OPG is a decoy circulating receptor for RANKL which blocks its binding to RANK. There are at least three mechanisms by which myeloma cells affects the OPG/ RANKL/RANK system: 1: The adhesion between the myeloma / stromal cells and the osteoblastic precursors stimulates the system by increasing the production of RANKL. 2: Some myeloma lines produce independently membrane-bound or free RANKL. 3: The normal and mutated plasma cells bind, degrade and block the OPG production from the stromal cells. The OPG/RANKL/RANK system is the latest therapeutic target in the treatment of myeloma bone disease. The first results from the application of a synthetic analogue of OPG, as well as of RANKL antagonists or RANK inhibitors show decrease of the number of osteoclasts, osteolytic lesions and M-gradient.
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PMID:Bone lesions in multiple myeloma--the OPG/RANK-ligand system. 1581 51

Gaucher disease is a lysosomal storage disorder, in which undigested glucosylceramide is deposited in the cytoplasm of mature macrophages, which accumulate in the bone marrow and the reticuloendothelial system. Dendritic cells are bone marrow-derived cells, specialized for the uptake, processing, transport and presentation of antigens to T-lymphocytes. We investigated peripheral blood dendritic cell-precursors, as well as the potential of peripheral blood monocytes and bone marrow-derived progenitor cells, to differentiate into mature dendritic cells in 12 patients with type I Gaucher disease. Results of the 10 adult patients were compared with those of 10 healthy volunteers, matched for age and sex. Six patients were anemic and 9 were thrombocytopenic, but none had severe bone disease. Both myeloid and plasmacytoid dendritic cells of patients with Gaucher disease, as well as the yield of the monocyte-derived dendritic cells, obtained after GM-CSF and IL-4 stimulation, were found significantly decreased, when compared to controls (myeloid dendritic cells: 0.19 +/- 0.07% vs. 0.34 +/- 0.10%, P = 0.009, plasmacytoid dendritic cells: 0.17 +/- 0.12% vs. 0.39 +/- 0.13%, P = 0.004, monocyte-derived dendritic cells: 4.8 +/- 3.5% vs. 8.3 +/- 3.2%, P = 0.036). However, the immunophenotypic profile of dendritic cells, estimated by CD1a, CD40, CD54, CD80, CD83 and HLA-DR expression, the endocytic and allo-stimulatory capacity of the immature, as well as of the TNF-alpha- or lipopolysaccharite-stimulated mature monocyte-derived dendritic cells, was similar to those obtained by healthy controls. In addition, bone marrow-derived CD34+ cells differentiated in the presence of GM-CSF, SCF, TNF-alpha and IL-4 into mature dendritic cells that did not differ in number, phenotype and allo-stimulatory activity from those of controls. Our findings suggest that patients with Gaucher disease exhibit mainly quantitative defects of their dendritic cells' system, demonstrated by decreased circulating dendritic cell precursors of both myeloid and plasmacytoid type. This finding may contribute to the poor immune response against infectious agents and an impaired immune surveillance, associated with an increased risk of developing a neoplastic disease.
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PMID:Dendritic cells in patients with type I Gaucher disease are decreased in number but functionally normal. 1653 13

IL-1alpha transgenic (Tg) mice exhibit chronic inflammatory arthritis and subsequent osteopenia, with IL-1-induced GM-CSF playing an important role in the pathogenesis. This study analyzed the mechanisms underlying osteopenia in Tg mice, and the therapeutic effects of the cyclooxygenase-2 inhibitor celecoxib on such osteopenia. Inhibited osteoclast formation was observed in RANKL-treated bone marrow cell (BMC) cultures from Tg mice and coculture of Tg-derived BMCs and wild-type-derived primary osteoblasts (POBs). FACS analysis indicated that this inhibition was attributable to a decreased number of osteoclast precursors within Tg-derived BMCs. Moreover, in coculture of Tg-derived POBs and either Tg- or wild-type-derived BMCs, osteoclast formation was markedly inhibited because Tg-derived POBs produced abundant GM-CSF, known as a potent inhibitor of osteoclast differentiation. Histomorphometric analysis of Tg mice revealed that both bone formation and resorption were decreased, with bone formation decreased more prominently. Interestingly, administration of celecoxib resulted in further deterioration of osteopenia where bone formation was markedly suppressed, whereas bone resorption remained unchanged. These results were explained by our in vitro observation that celecoxib dose-dependently and dramatically decreased osteogenesis by Tg mouse-derived POBs in culture, whereas mRNA expressions of GM-CSF and M-CSF remained unchanged. Consequently, blockade of PGE(2) may exert positive effects on excessively enhanced bone resorption observed in inflammatory bone disease, whereas negative effects may occur mainly through reduced bone formation, when bone resorption is constitutively down-regulated as seen in Tg mice.
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PMID:Administration of cyclooxygenase-2 inhibitor reduces joint inflammation but exacerbates osteopenia in IL-1 alpha transgenic mice due to GM-CSF overproduction. 1757 86

IL-27 was first discovered as a factor supporting initial Th1 immune responses. Subsequent studies revealed that this cytokine has pleiotropic effects, including inhibition of certain immune cells, a regulatory role in hemopoietic stem cell differentiation, and antitumor activities. However, the role of human IL (hIL)-27 in human osteoclast precursors and inflammatory bone disease is unclear. Here, we examined the direct effect of hIL-27 on human osteoclastogenesis. Human bone marrow cells cultured in MethoCult medium containing human (h) GM-CSF, human stem cell factor, and hIL-3 expressed Mac-1, c-kit, and c-Fms. These cells, called hCFU-GMs, also expressed the IL-27 receptor, an IL-27Ralpha (WSX-1)/gp130 heterodimer. Cultivation in hM-CSF and human receptor activator of NF-kappaB ligand induced the differentiation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) from hCFU-GMs, and hIL-27 inhibited this osteoclastogenesis in a dose-dependent manner. hIL-27 also repressed bone resorption by osteoclasts on a dentine slice. hIL-27 caused a remarkable increase in STAT1 phosphorylation and enhanced the STAT1 protein level. It also inhibited the expression of receptor activator of NF-kappaB ligand-induced c-Fos and cytoplasmic, calcineurin-dependent 1 NFAT (NFATc1), which are indispensable transcription factors for osteoclastogenesis. Fludarabine, a STAT1 inhibitor, and STAT1 small interfering RNA partially rescued the inhibition of osteoclastogenesis by IL-27. A WSX-1 deficiency caused severe inflammatory bone destruction primed by Escherichia coli cell wall lysate in vivo. Therefore, hIL-27 may act as an anti-inflammatory cytokine in human bone destruction, by inhibiting osteoclastogenesis from hCFU-GMs via STAT1-dependent down-regulation of the transcription factor c-Fos. Our results suggest that hIL-27 may prove useful as a therapeutic target for inflammatory bone destruction.
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PMID:IL-27 abrogates receptor activator of NF-kappa B ligand-mediated osteoclastogenesis of human granulocyte-macrophage colony-forming unit cells through STAT1-dependent inhibition of c-Fos. 1962 Mar 1


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