Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Active vitamin D metabolites are not only involved in the regulation of bone metabolism but exerts immunomodulatory effects important in the regulation of inflammatory processes. The purpose of the present study was to evaluate the effects of a short-time treatment with 1 alpha-hydroxycholecalciferol on both disease activity and bone metabolism in patients with rheumatoid arthritis (RA). The effects of an adjuvant therapy with 1 microgram 1 alpha-hydroxycholecalciferol over eight weeks on conventional parameters of disease activity (Ritchie index, duration of morning stiffness, C-reactive protein, ESR), serum levels of cytokines and soluble cytokine receptors (TNF-alpha, IL-6, IL-4, sIL-2R, sIL-6R) and parameters of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, renal excretion of pyridinolin- and desoxypyridinolin-collagen-crosslinks, serum levels of parathormon, 1,25-dihydroxycholecalciferol and calcium, daily urinary calcium excretion) were investigated in 20 patients with RA. The treatment with 1 alpha-hydroxycholecalciferol resulted in an insignificant decrease in the number of swollen and tender joints, morning stiffness, CRP and ESR. Furthermore, a non-significant decrease in serum levels of TNF-alpha and IL-6 and an increase in IL-4 was observed. The treatment led to a significant decrease of bone-specific alkaline phosphatase (p = 0.001), osteocalcin (p = 0.04) and renal excretion of pyridinolin-crosslinks (p = 0.022) and to an increase of both serum calcium (p = 0.01) and daily urinary calcium excretion (p = 0.004). The results of this pilot study in a small group of RA patients indicate that an adjuvant therapy with active vitamin D metabolites may not only have preventive effects on systemic bone loss but also may inhibit the inflammatory and destructive process in RA in a limited degree.
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PMID:[Vitamin D metabolites in rheumatoid arthritis: findings--hypotheses--consequences]. 1076 32

We describe efficient methods for using functional proteomics analysis to study signal transduction pathways in murine fibroblast L929 cells following stimulation with tumor necrosis factor (TNF)-alpha. After stimulation with TNF-alpha, cellular proteins of L929 cells were extracted with a lysis buffer containing 0.3% sodium dodecyl sulfate (SDS) for 10-30 min time intervals, and were separated by two-dimensional (2-D) electrophoresis followed by immunoblot analysis with anti-phosphotyrosine antibody and alkaline phosphatase-anti IgG antibody conjugate. To improve detection sensitivity by immunoblot analysis we used a chemifluorescent substrate for alkaline phosphatase. One hundred protein spots were detected in the TNF-alpha stimulated L929 cell extract by immunoblot analysis. The use of chemifluorescence allowed us to quantitate immunoblotted spots with fluoroscanner so that we were able to detect time-dependent changes of a number of immunoblotted spots. Protein spots on a silver-stained 2-D gel corresponding to those detected by immunoblot analysis were subjected to in-gel trypsin digestion- matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-mass spectrometry analysis, respectively. Twenty-one proteins detected by immunoblot analysis were identified by MS-Fit database search analysis. Among them, the proteins that show time-dependent changes in staining intensity include vimentin, tubulin beta-chain, eukaryotic translation initiation factor 1A, chromatin assembly factor 1 (P48 subunit), probable protein disulfide isomerase P5, and several other proteins. Vimentin and tubulin beta-chain have been reported to be phosphorylated at tyrosine residues and involved in the signal transduction pathway induced by TNF-alpha. However, the other proteins have no previously known function in the signal transduction pathway. Thus, the methods used in this study seem to be suitable for the identification of time-dependent changes in many proteins that are involved in signal transduction. Usefulness of the method for comprehensive analysis of the proteins involved in signal transduction pathway and the limitations of the method are discussed.
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PMID:Matrix assisted laser desorption/ionization-time of flight-mass spectrometry analysis of proteins detected by anti-phosphotyrosine antibody on two-dimensional-gels of fibrolast cell lysates after tumor necrosis factor-alpha stimulation. 1087 Sep 74

To clarify the role of tumor necrosis factor (TNF)-alpha on osteoblast functions in the presence of metal particles, two human osteoblast-like cell lines (MG-63 and SaOS-2) were cultured with TNF-alpha in the presence or absence of titanium particles in vitro. A combination of TNF-alpha and titanium particles showed additive effects on inhibition of cell proliferation and alkaline phosphatase production. On the other hand, production of interleukin-6, which is well known to induce osteoclastogenesis and to directly stimulate bone resorption, was additively stimulated by the combination of TNF-alpha and titanium particles. These results suggest that the association of TNF-alpha and titanium particles may play an important role in the pathogenesis of periprosthetic osteolysis through two different pathways: a reduced periprosthetic bone formation due to inhibition of osteoblast proliferation and alkaline phosphatase production, and osteoblast-mediated activation of osteoclastic bone resorption as suggested by the enhancement of interleukin-6 production.
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PMID:Combined effect of titanium particles and TNF-alpha on the production of IL-6 by osteoblast-like cells. 1095 79

Curcumin, an anti-inflammatory, antioxidant, was evaluated for its ability to suppress bleomycin (BLM)-induced pulmonary fibrosis in rats. A single intratracheal instillation of BLM (0.75 U 100(-1) g, sacrificed 3, 5, 7, 14 and 28 days post-BLM) resulted in significant increases in total cell numbers, total protein, and angiotensin-converting enzyme (ACE), and alkaline phosphatase (AKP) activities in bronchoalveolar lavage fluid. Animals with fibrosis had a significant increase in lung hydroxyproline content. Alveolar macrophages from BLM-administered rats elaborated significant increases in tumour necrosis factor (TNF)-alpha release, and superoxide and nitric oxide production in culture medium. Interestingly, oral administration of curcumin (300 mg kg(-1) 10 days before and daily thereafter throughout the experimental time period) inhibited BLM-induced increases in total cell counts and biomarkers of inflammatory responses in BALF. In addition, curcumin significantly reduced the total lung hydroxyproline in BLM rats. Furthermore, curcumin remarkably suppressed the BLM-induced alveolar macrophage production of TNF-alpha, superoxide and nitric oxide. These findings suggest curcumin as a potent anti-inflammatory and anti-fibrotic agent against BLM-induced pulmonary fibrosis in rats.
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PMID:Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats. 1099 7

Extensive studies have been performed to evaluate different factors that may affect on spinal interbody fusion, but the role of intervertebral disc tissue in the fusion process remains unclear. To study the influence of intervertebral disc tissue on osteoblast metabolism, we harvested disc tissue from patients who had undergone spinal surgery. The nucleus pulposus and annulus fibrosus were separately co-cultured with osteoblast-like cells SaOS-2 by means of culture inserts or organ culture. We assayed alkaline phosphoatase activity, 3H-thymidine incorporation into the DNA, and production of collagen type I, IL-1beta, IL-6, IL-10, and TNF-alpha. Exposure of the nucleus pulposus (NP) to osteoblast-like cells revealed stimulation of alkaline phosphatase production, 3H-thymidine incorporation and collagen type I production. Exposure of the annulus fibrosus (AF) stimulated 3H-thymidine incorporation and collagen type I production, but did not affect ALP activity. IL-6 was detected after application of NP and AF. Interleukin IL-10, IL-1beta and TNF-alpha were all below detection levels after application of disc tissue. Our findings show that frozen disc tissue stimulates the metabolism of osteoblast-like cells in vitro.
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PMID:The influence of human intervertebral disc tissue on the metabolism of osteoblast-like cells. 1118 9

The present study has been undertaken to evaluate bone turn-over in rheumatoid arthritis (RA) patients as well as the influence of low dose glucocorticosteroids (gcs) on bone mass loss. Ninety patients with establish RA has been investigated. The patients have been divided into two groups: 44 patients treated with gcs (age 52.5 +/- 12.4 years, disease duration 122 +/- 102 months, total dose of GCS, equivalent to prednisone -7.4 +/- 8.3 g) and 46 patients who were not treated with gcs (age 54.3 +/- 9.7 years, disease duration 134 +/- 120 month). Fifty patients have been assessed twice (after 12 month). Bone mineral content and bone mineral density have been determined in all patients in distal forearm. Additionally, some biochemical markers of osteoporosis: osteocalcin, alkaline phosphatase-bone formation, carboxyterminal telopeptides of type I collagen (CTx), procollagen type I carboxyterminal propeptide (PICP), deoxypyridynoline and some proinflammatory cytokine: IL-1 alpha, IL-6, TNF-alpha, GM-CSF has been determined. No difference in bone metabolism between RA patients receiving gcs treatment and those treated without gcs was shown. It is concluded that anti-inflammatory effect of gcs may balance the direct effect of gcs on bone mineral content in RA patients, particularly those with short term treatment.
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PMID:[Bone tissue metabolism in patients with rheumatoid arthritis treated with glucocorticosteroids]. 1130 11

Renal osteodystrophy is a metabolic bone disease occurring in patients with end-stage renal failure. The aim of the study was to compare serum concentrations of some bone markers in hemodialysed (HD) patients and in patients undergoing continuous ambulatory peritoneal dialysis (CADO). We studied two groups of patients with end-stage renal failure: 52 hemodialysed individuals aged 24-74 years and 19 peritoneally dialysed patients aged 20-70 years. Serum calcium and phosphate concentration, cholesterol, triglycerides, total protein, albumin, alkaline phosphatase, urea before and after HD, urea in CADO patients were determined by standard laboratory methods. Serum PTH, osteocalcin, 1,25(OH)2D3 and insulin-like growth factor (IGF-1) concentrations were measured by commercially available radioimmunoassay. Serum tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1) concentrations were measured by ELISA. There were no differences between serum concentrations of the studied bone markers in hemodialysed patients and CAPD patients. All dialysed patients presented high concentrations of serum PTH, osteocalcin, alkaline phosphatase activity, lower serum IGF-1 concentration and normal serum calcitriol concentration. High serum PTH and osteocalcin concentrations may indicate intensification of bone synthesis, what is typical for osteitis fibrosa.
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PMID:[Selected parameters of bone metabolism in hemodialyzed and peritoneally dialyzed patients]. 1139 92

Cytokines and nitric oxide (NO) have been implicated in bone loss caused by estrogen deficiency. Here we evaluated the effect of nitric oxide synthase (NOS) inhibitors on the bone particle resorbing activity and TNF-alpha release of cultured peripheral blood monocytes (PBM) obtained from 10 premenopausal (PreM) and 10 postmenopausal (PostM) women. Gonadal status (menopause < 3 yr) was assessed by FSH and estradiol. Bone alkaline phosphatase and N-Telopeptide were significantly increased in PostM. Significant differences between PreM and PostM women were observed in bone mineral density of lumbar spine. The bone particle resorbing activity of PBM cultured in the presence of L-arginine-methyl ester (NAME) or aminoguanidine, NOS inhibitors, was determined by (45)Ca release from rat bone labeled particles. TNF-alpha release was assayed in supernatants by ELISA. (45)Ca release was higher in PostM (p < 0.01) and was enhanced by NAME (p < 0.02). Furthermore, TNF-alpha release from PBM was significantly higher in PostM (p < 0.01). Aminoguanidine significantly increased TNF-alpha release in PreM. Based on these findings and on the evidence that estrogen stimulates NOS, we suggest that estrogen withdrawal may reduce the inhibitory effect of NO on TNF-alpha release. Thus, this increased production of TNF-alpha could contribute to the increased postmenopausal bone turnover.
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PMID:Estrogenic status influences nitric oxide-regulated TNF-alpha release from human peripheral blood monocytes. 1157 73

Bone wound healing requires osteoinductive signals that are attributed to (the) bone morphogenetic proteins (BMPs). The cellular origin of such osteoinductive signals has only been partially elucidated. Because of the central role of the macrophage in cutaneous wound healing, we hypothesized that the macrophage could play a similar role in osseous healing. It was the aim of the present investigation to examine the possible expression of BMP by the macrophage, and to evaluate the contribution of macrophage products to an early step of bone formation modeled in an in vitro culture system. The synthesis of BMP-2 and BMP-6 by cultured human and murine macrophages was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). When human mesenchymal stem cells (hMSCs) were grown in conditioned media from J774A.1 cells, alkaline phosphatase expression increased. This induction was blocked by anti-BMP-2 antibody and by anti-transforming growth factor-beta1 (TGF-beta1) antibody. Modeling of the macrophage expression of osteoinductive signals by potential physiological situations was evaluated by treatments with lipopolysaccharide (LPS) or macrophage chemotactic peptide-1 (MCP-1). Macrophage BMP-2 expression was reduced by proinflammatory LPS stimulation (which was confirmed to induce release of the proinflammatory cytokine, TNF-alpha), and conditioned media from LPS-treated macrophages had no ability to increase alkaline phosphatase activity in hMSCs. This first study of macrophage BMP-2 expression indicates that the macrophage is capable of physiological regulation consistent with a key role in osteoinduction for osseous wound healing.
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PMID:Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. 1179 61

Myelomatous bone disease affects about 90% patients with multiple myeloma and solitary myeloma as well. In initial stage it is manifested as osteopenia with osteoporosis or osteolytic foci, pathologic fractures followed by neurologic complications. Ethiopathogenitically a role is played by cytokine interactions with local chemokines produced by myeloma cells and activated stromal and hemopoietic cells (osteoblasts, monocytes, macrophages) resp. From the TNF-alpha family glycoprotein complexes are liberated (RANK-L), which support activation and proliferation or are inhibitory (osteoprotegerins). Similarly in the family TGF-beta several izotypes of antiinflammatory cytokines are known (the most important is TGF-beta 1 and the morphogenetic protein-2), which have a fibrotizing effect in bones, because the produced osteoid is insufficiently mineralized. The effect is a pathologic remodelation of the skeleton. In the diagnosis of multiple myeloma the immunological knowledge is used in the initial diagnosis (immunophenotypization, follow up of TNF-alpha, TGF-beta 1, IL-1, IL-6 etc). Important are also biochemistry values of increased osteoresorption (changes of calcium, parathormone, excretion of collagen fission products, osteocalcin, the bone alkaline phosphatase). In the following part the authors inform about favourable results of long-term treatment with bisphosphonates (Bonefos, Ibandronate) in combination with anti-tumor chemotherapy in 364 patients. During a 15 years observation period median survival of 94 months with a 35% probability of 10 year survival was achieved with a significant decrease of bone complications in 58% compared to 14% in the placebo group.
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PMID:[Bone changes in multiple myeloma--current etiopathogenic, diagnostic and therapeutic aspects]. 1219 8


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