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)

The aim of this investigation was to determine whether some metabolic defect might be related to the propensity of osteoporotic femoral necks to fracture acutely. To this end, the activities of two dehydrogenases of the glycolytic Embden-Meyerhof pathway, two of the pentose phosphate pathway, two mitochondrial enzymes, and alkaline phosphatase were measured in the cortical and in the trabecular osteoblasts. Comparison was made with such activities in iliac crest biopsies from patients with these fractures and from the equivalent femoral and iliac crest samples from patients with osteoarthritis of the hip, in biopsies from the iliac crests from seven patients with no bony abnormality, and in specimens from the fracture site of six traumatic fractures. The results showed a highly significant decrease in the activities of the two enzymes of the pentose phosphate pathway (p less than 0.001) in the cortical, but not in the trabecular, osteoblasts in the osteoporotic fractures. This could not be attributed to the trauma of acute fracture since it was not found in traumatic fractures. Other experimental evidence has indicated that a relationship may occur between depressed activity of these enzymes and a retardation of bone formation.
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PMID:Selective depression of metabolic activities in cortical osteoblasts at the site of femoral neck fractures. 239 Mar 73

A procedure was developed to investigate the electrolyte metabolism of human trabecular bone and its regulation in vitro, in particular the influence of prostaglandins. Trabecular bone was prepared from femoral heads of patients who had undergone hip replacement surgery for coxarthrosis. 500 mg samples were incubated in modified EAGLE's minimal essential medium. Net electrolyte movements between bone and incubation medium were measured. During 6 hours of incubation PGE2 caused an increase in the release of calcium and magnesium from bone into incubation medium as compared to controls. The effect of PGE2 was dose-dependent and comparable to that of human parathyroid hormone 1-34 (hPTH 1-34) whereas hPTH 3-34 had no effect. Human calcitonin (hCT) caused a decrease in the release of calcium and magnesium. PGE2 was found to be the most potent prostaglandin. PGE1 and PGF2 alpha had about 50% and PGF1 alpha about 40% of the potency of PGE2. PGA1 and PGA2 had no effect. The effect of PGE2 could be completely inhibited by hCT and was not further enhanced by hPTH 1-34. Magnesium movement was affected in the same way as calcium movement, while phosphate movement and release of alkaline phosphatase and hydroxyproline from bone into incubation medium were not affected by prostaglandins.
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PMID:Influence of prostaglandins on electrolyte metabolism of human trabecular bone in vitro. 659 50

Prostaglandins seem to be involved in the pathogenesis of juxtaarticular osteopenia in rheumatoid arthritis. Therefore the influence of prostaglandins on in vitro electrolyte metabolism of human trabecular bone was tested. Trabecular bone was prepared from femoral heads of patients who had undergone hip replacement surgery for coxarthrosis. 500 mg samples of trabecular bone were incubated in modified Eagle's minimal essential medium. Net electrolyte movements between bone and incubation medium were measured. PGE2 caused an increase in the release of calcium (Ca) and magnesium (Mg) from bone into incubation medium as compared to controls (PGE2 1 micrograms/ml: Ca = 0.87 +/- 0.09 mmol/l*, Mg = 0.44 +/- 0.03 mmol/l*; controls: Ca = 0.81 +/- 0.09 mmol/l, Mg = 0.41 +/- 0.05 mmol/l; n = 15, *p less than 0.001). The effect of PGE2 was dose-dependent and comparable to the effect of human parathyroid hormone 1-34 (hPTH 1-34). PGE2 turned out to be the most potent prostaglandin on human trabecular bone. PGE1 and PGF2 alpha had about 50% and PGF1 alpha about 40% of the potency of PGE2. PGA1 and PGA2 had no effect. The effect of PGE2 could be completely inhibited by human calcitonin (hCT), similar to the inhibition of the effect of hPTH 1-34 by hCT. The effect of PGE2 was not further enhanced by hPTH 1-34. Magnesium metabolism was affected in all experiments in the same way as calcium metabolism. Phosphate metabolism, release of alkaline phosphatase and hydroxyproline from bone into incubation medium were not affected by prostaglandins.
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PMID:[Effect of prostaglandins on in vitro electrolyte metabolism in human spongiosa]. 659 15

Remodeling imbalance in the elderly femoral neck can result in thin cortices and porosity predisposing to hip fracture. Hip osteoarthritis protects against intracapsular hip fracture. By secreting sclerostin, osteocytes may inhibit Wnt signaling and reduce bone formation by osteoblasts. We hypothesised that differences in osteocytic sclerostin expression might account for differences in osteonal bone-formation activity between controls and subjects with hip fracture or hip osteoarthritis. Using specific antibody staining, we determined the osteocytic expression of sclerostin within osteons of the femoral neck cortex in bone removed from subjects undergoing surgery for hip osteoarthritis (hOA: 5 males, 5 females, 49 to 92 years of age) or hip fracture fixation (FNF: 5 males, 5 females, 73 to 87 years of age) and controls (C: 5 males, 6 females, 61 to 90 years of age). Sclerostin expression and distances of each osteocyte to the canal surface and cement line were assessed for all osteonal osteocytes in 636 unremodeled osteons chosen from fields ( approximately 0.5 mm in diameter) with at least one canal staining for alkaline phosphatase (ALP), a marker of bone formation. In adjacent sections, ALP staining was used to classify basic multicellular unit (BMUs) as quiescent or actively forming bone (ALP(+)). The areal densities of scl(-) and scl(+) osteocytes (number of cells per unit area) in the BMU were inversely correlated and were strong determinants of ALP status in the BMU. In controls and hip fracture patients only, sclerostin-negative osteocytes were closer to osteonal surfaces than positively stained cells. Osteon maturity (progress to closure) was strongly associated with the proportion of osteonal osteocytes expressing sclerostin, and sclerostin expression was the chief determinant of ALP status. hOA patients had 18% fewer osteocytes per unit bone area than controls, fewer osteocytes expressed sclerostin on average than in controls, but wide variation was seen between subjects. Thus, in most hOA patients, there was increased osteonal ALP staining and reduced sclerostin staining of osteocytes. In FNF patients, newly forming osteons were similar in this respect to hOA osteons, but with closure, there was a much sharper reduction in ALP staining that was only partly accounted for by the increased proportions of osteonal osteocytes staining positive for sclerostin. There was no evidence for a greater effect on ALP expression by osteocytes near the osteonal canal. In line with data from blocking antibody experiments, osteonal sclerostin appears to be a strong determinant of whether osteoblasts actively produce bone. In hOA, reduced sclerostin expression likely mediates increased osteoblastic activity in the intracapsular cortex. In FNF, full osteonal closure is postponed, with increased porosity, in part because the proportion of osteocytes expressing sclerostin increases sharply with osteonal maturation.
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PMID:Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture. 2020 Sep 87

Bone diseases represent an increasing health burden worldwide, and basic research remains necessary to better understand the complexity of these pathologies and to improve and expand existing prevention and treatment approaches. In the present study, 216 bone samples from the caput femoris and collum femoris of 108 patients with degenerative or dysplastic coxarthrosis, hip fracture, or osteonecrosis were evaluated for the proportion of trabecular bone (TB) and expression of parathyroid hormone (PTH) type 1 receptor (PTH1R), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Serum levels of PTH, OPG, soluble RANKL (sRANKL), alkaline phosphatase (AP), osteocalcin, total procollagen type-1 intact N-terminal propeptide (TP1NP), tartrate-resistant acid phosphatase type 5b (TRAP5b), sclerostin, and C-telopeptide of type-1 collagen (ICTP) were also determined. Age was positively correlated with serum levels of PTH, OPG, and sclerostin but negatively associated with TB and sRANKL. Women exhibited less TB, lower sclerostin and ICTP, and higher TRAP5b. Impaired kidney function was associated with shorter bone decalcification time, less TB, lower sRANKL, and higher serum PTH, OPG, and sclerostin. Furthermore, correlations were observed between bone PTH1R and OPG expression and between serum PTH, OPG, and AP. There were also positive correlations between serum OPG and TP1NP; serum OPG and sclerostin; serum AP, osteocalcin, and TRAP5b; and serum sclerostin and ICTP. Serum OPG was negatively associated with sRANKL. In summary, clear relationships between specific bone metabolism markers were observed, and distinct influences of age, sex, and kidney function, thus underscoring their suitability as diagnostic or prognostic markers.
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PMID:Comprehensive assessment of tissue and serum parameters of bone metabolism in a series of orthopaedic patients. 3188 Oct 44