Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms involved in juxta-articular bone destruction are poorly understood. Osteocalcin or gamma-carboxyglutamic acid (GLA) protein is a small non-collagenous bone protein. It is a sensitive marker of osteoblastic bone formation. Its seric variations in the serum in such rheumatisms as rheumatoid arthritis remain unclear. Further information on local osteoblastic activity may be obtained by assaying the level of osteocalcin in the synovium. Its serum level can be evaluated by radioimmunoassay. The same method can be used in the synovial fluid. Paired serum and synovial fluid samples have been assayed from 63 patients, 33 patients with inflammatory arthritis (rheumatoid arthritis, psoriasis, chondrocalcinosis, pyogenic arthritis) and 30 patients with mechanical joint effusion (osteoarthritis, meniscal lesions). Serum levels of osteocalcin were the same in the inflammatory group (m: 8.69 +/- 0.68 ng/ml) and in the mechanical group (m: 10.2 +/- 0.67 ng/ml). In the synovial fluid, the levels of osteocalcin were significantly lower in the inflammatory group (m: 3.27 +/- 0.40 ng/ml) than in the mechanical group (m: 6.91 +/- 0.47 ng/ml). The same results were obtained with the ratio of synovial fluid osteocalcin on serum osteocalcin. There was a significant correlation between serum and synovial fluid osteocalcin and an inverse correlation between synovial fluid osteocalcin and the number of synovial fluid cells. The present study suggests that periarticular osteoblastic depression, among patients with inflammatory arthritis, is likely.
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PMID:Serum and synovial fluid osteocalcin in rheumatic diseases. 147 75

Recent studies indicate that the mode of action of estrogen in preventing bone loss due to ovarian hormone deficiency may vary with the dose of the hormone. In this study four groups of ovariectomized animals were maintained on a wide range of doses of 17 beta-estradiol to further determine the relationship of dose to the mechanism by which estrogen prevents ovarian hormone deficiency bone loss. Ovariectomy caused a significant decrease in bone density and cancellous bone volume at the proximal metaphysis of the tibia. The decrease was prevented in a dose-dependent manner by estradiol. The rate of bone apposition in cancellous bone in the proximal tibia was increased by ovariectomy, and inhibited in a dose-dependent manner by estradiol. Similarly, ovariectomy increased the excretion of urinary hydroxyproline, an index of the rate of bone turnover, and serum alkaline and tartrate-resistant acid phosphatase. The increases were prevented in a dose-dependent manner by estradiol. In addition, the very high dose of estradiol, but not the lower doses, caused a marked (50%) decrease in serum osteocalcin. Our interpretation of these findings is that the low to very high doses of estradiol used in this study decreased the progression of the bone loss due to ovariectomy by suppression of the rate of bone turnover that involved the depression of both osteoclastic resorption and osteoblastic bone formation.
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PMID:Skeletal response of ovariectomized rats to low and high doses of 17 beta-estradiol. 193 91

Osteoporosis and epiphyseal aseptic bone necrosis are side-effects of corticosteroid therapy that must be detected and prevented. The incidence of osteoporosis depends on whether radiology or densitometry are used for its evaluation. Bone loss is accounted for by osteoblast depression and decreased intestinal absorption of calcium, responsible for secondary hyperparathyroidism. The clinical progress of steroid-induced osteoporosis is often impressive. Plasma osteocalcin levels are lowered. Nowadays, non-invasive methods of bone mass measurement are indispensable for detection and follow-up. Prevention rests on adjustment of corticosteroid therapy and, above all, on the prescription of calcium and vitamin D; fluoride constitutes the curative treatment. Corticosteroid dosage plays a role in the occurrence of aseptic bone necrosis at an early stage of treatment. The lesions, often multiple and progressive, mostly affect the femur. MRI is the most sensitive examination for early detection. When medical treatment has failed, total hip replacement may be considered.
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PMID:[Bone and osteo-articular complications of corticotherapy]. 232 Aug 82

Osteocalcin is a vitamin K-dependent protein that is synthesized by osteoblasts and present in circulation. We measured serum osteocalcin concentrations in nine asthmatics before and during treatment with high IV dosages of glucocorticoids, betamethasone 0.65 mg/h. This treatment induced within 13 +/- 1.5 (SEM) hours a reduction of serum osteocalcin form 2.6 +/- 0.3 (SEM) to 1.2 +/- 0.3 microgram/L (P less than .001). During the following 24-hour period the osteocalcin levels further declined and reached a level about 30% of the pretreatment level. Continued treatment did not induce a further reduction of serum osteocalcin. A positive correlation was seen between the pretreatment osteocalcin concentration and the steady-state osteocalcin value during steroid therapy. The corticosteroids did not influence the serum calcium and phosphate concentrations but induced a minor, significant (P less than .001) decrease of serum alkaline phosphatase. After completion of steroid therapy, the osteocalcin values remained depressed for another 24 hours but had reached the pretreatment levels after another three days. Our data suggest osteocalcin as a sensitive marker of the corticosteroid induced depression of osteoblast activity.
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PMID:The acute effect of high dose corticosteroid treatment on serum osteocalcin. 325 42

Osteocalcin (a vitamin K-dependent, bone-specific protein) is widely accepted as a marker of osteoblastic activity. The present study was conducted to determine if a vitamin K deficiency would affect fracture healing by virtue of an alteration in osteocalcin metabolism. Thirty male Sprague-Dawley rats were divided into two groups. The control group was fed a diet that was lacking in, but offered water replete with vitamin K. The experimental group was fed a vitamin K-deficient diet and was offered water that was lacking in vitamin K. After two weeks, vitamin K deficiency was established in the experimental group as shown by decreased urinary excretion of gamma-carboxyglutamic acid and an elevation of serum prothrombin times to between two to two and one-half times the control values. At this time, a standard, closed femoral fracture was produced. Six weeks later, the animals were killed. The bones were biomechanically tested in torsion. Subsequent to mechanical testing, the calluses were retrieved, and the osteocalcin content and the degree of gamma carboxylation of the osteocalcin in the calluses were measured. The results show that despite significant alterations in the gamma carboxylation of osteocalcin and elevation of prothrombin times to two to two and one-half times the control values, there were no differences in the mechanical properties of the calluses. Furthermore, there were no differences in the content or gamma carboxylation of osteocalcin in these calluses. Apparently, in vitamin K deficiency, fracture callus achieves normal mechanical properties and may have a mechanism for the gamma carboxylation of glutamic acids in osteocalcin despite a substantial depression of this activity in the rest of the body.
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PMID:Fracture healing and osteocalcin metabolism in vitamin K deficiency. 326 5

Serum osteocalcin (OC) levels were measured in 19 asthmatic patients receiving long term glucocorticoid therapy and in age- and sex-matched asthmatic patients not receiving this treatment. In the glucocorticoid-treated patients, the mean OC level was approximately 50% less than that in the control group (P less than 0.001), and there was a direct correlation between serum OC and 1,25-dihydroxyvitamin D [1,25-(OH)2D; r = 0.71; P less than 0.001]. Multiple regression analysis in a total of 39 glucocorticoid-treated patients indicated that OC correlated directly to 1,25-(OH)2D and inversely to glucocorticoid dose. There was no correlation between OC and 1,25-(OH)2D in the control group and no significant difference in mean serum 1,25-(OH)2D between the steroid-treated asthmatic patients and the asthmatic control patients. The effect of a 4-day course of oral 1,25-(OH)2D on serum OC was studied in six patients with glucocorticoid excess and six normal subjects. There was a similar percent increase in OC levels in both groups, though the basal concentrations and absolute increases were substantially less in the steroid-treated group. It is likely that the depression of serum OC in glucocorticoid-treated patients results from the reduction in the rate of bone formation induced by these hormones.
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PMID:Low serum osteocalcin levels in glucocorticoid-treated asthmatics. 348 82

Smoking is a risk factor for osteoporosis. Nicotine and nonnicotine tobacco smoke components have been shown to depress osteoblast activity in a number of in vitro and animal studies. To determine whether smoking is associated with depressed osteoblast activity in humans, we measured serum osteocalcin levels (using a radioimmunological method based on an antibody to human osteocalcin) in 24 male or female smokers and 24 matched nonsmokers. Overall, osteocalcin levels were significantly lower in smokers (15 +/- 6.95 ng/ml) than in nonsmokers (21.27 +/- 8.34 ng/ml) (p = 0.007). The difference between smokers and nonsmokers was significant in males (15.3 +/- 4.5 vs 23.27 +/- 9.7; p = 0.02) but not in females (16.27 +/- 8.9 vs 19.45 +/- 6.7; p = 0.2). These data suggest that smoking may induce osteoblast depression, either directly or via hormonal changes.
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PMID:[Osteocalcin and smoking]. 783 68

A 56-year-old white man was referred for evaluation of severe hypercalcemia following a three-week history of progressive weakness, nausea, and depression. Initial laboratory results showed serum total and ionized calcium (Ca++) values of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately performed and an extremely high value was obtained in just 30 min (1315 ng/l, normal values 6.4-70.4). The patient was therefore treated with saline solution and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and intact PTH during the first six days; then there was a trend to reach a steady-state until parathyroidectomy was performed. After withdrawal of calcitonin therapy it was possible to observe a positive uncoupling between bone formation (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate-resistant acid phosphatase) markers. On day 35 the patient underwent neck exploration, and an enlarged lower left parathyroid gland was removed that on macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic appearance was suggestive of a previous glandular infarction. This is the first time the daily clinical course of a parathyroid crisis has been documented. Furthermore, changes of biomarkers of bone turnover following calcitonin therapy show that high doses of the hormone may cause a prolonged positive uncoupling of the two processes of bone remodeling.
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PMID:Parathyroid storm: immediate recognition and pathophysiological considerations. 826 42

Osteoblastic cells respond to mechanical stimuli with alterations in proliferation and/or phenotypic expression. In some cases, these responses occur within only a few applications of stimuli (i.e. 'cycle-dependent trigger response') rather than in a dose-dependent manner. To explore potential mechanisms of the cycle dependent trigger response, we raised the following questions: (1) Does strain of bone cells alter gene expression; if so, how quickly does it occur and how long does it last? (2) Are alterations in message level strain magnitude dependent? (3) Are alterations in steady-state message levels cycle dependent? Cultures were evaluated for osteocalcin mRNA one week following a daily stretch application at four stretch magnitudes and four cycle numbers and compared to nonstretched controls. Steady state mRNA message was ascertained prior to and at 10, 20, 30, 60, 120, 180, and 240 min following initiation of stretch. Following mRNA isolation, first strand cDNA synthesis was performed and fluorometrically quantitated. A reverse transcriptase based PCR (RT-PCR) approach allowed assessment of osteocalcin mRNA levels from microcultures (50,000 cells per 10 microliters culture or 5000 cells mm2) of rat calvarial osteoblasts. Optimized PCR was performed using primers to the bone specific protein, osteocalcin (OC) and two 'housekeeping' genes, beta-actin and GAP-DH. PCR products were separated on 4% agarose gels and band intensities digitized with relative quantitation based on internal standards in each gel. The lowest magnitude of stretch (- 1 KPa) at 1800 cycles per day reproducibly depressed message for osteocalcin, but not beta-actin when assayed immediately following the cessation of strain application. By three hours following the initiation of stretch, message levels returned to control values. At the time of stretch cessation, the 1800 cycle stretch regimen diminished (p < 0.0001) steady-state osteocalcin message independently of the four stretch magnitudes. Stretch for 300 cycles failed to depress (p = 0.05) osteocalcin message cultures at any time, but 600 cycles depressed message by 30 min. By one and two hours, cultures stretch 600, 900, and 1800 cycles showed similar levels of message depression. Four hours following the initiation of stretch, message levels returning to nonstrained levels in all groups. We conclude that alterations in cell response to strain are in part mediated by gene expression, that alterations last 3-4 h in this system, and that the message mechanism itself exhibits a trigger-response dependency to cycle number.
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PMID:Cellular deformation reversibly depresses RT-PCR detectable levels of bone-related mRNA. 866 82

The exact mechanisms by which mechanical loading-unloading affects bone tissue are mostly unknown. Recently, osteocalcin, a direct product of osteoblasts, has been shown to reflect the activity of the mineralization phase of the newly formed bone matrix, and therefore, the in situ detection of osteocalcin could be used for studying the effects of physical activity-inactivity on the osteoblast function or bone formation in the target bone. In this study, the effect of various loading states (immobilization and three forms of subsequent remobilization) on the in situ expression of osteocalcin in the rat patellas and their osteotendinous junctions was studied immunohistochemically using a polyclonal rat antiosteocalcin as the primary antibody. Following immobilization for 3 weeks, the immunoreactivity of osteocalcin was markedly decreased or was completely absent in all the patellar areas which normally show intense reaction as a sign of mineralization of the newly formed bone, that is, in the subperiosteal and subchondral regions, in the osteoid tissue that lies on the surface of the trabecular bone, and around the cortical lacunae. The same was true in the mineralized fibrocartilage zone of the osteotendinous junction of the quadriceps tendon. Free remobilization for 8 weeks (free cage activity) could not improve the situation, but after intensified remobilization of the same duration (low and especially high intensity treadmill running) high osteocalcin expression was observed in the above-mentioned anatomic sites. These findings indicate that formation of new bone tissue is rapidly regulated by the loading states of the bone. Higher than normal activity seems to be needed to restore the bone formation from the disuseinduced depression to normal.
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PMID:Expression of osteocalcin in the patella of experimentally immobilized and remobilized rats. 877 Jul


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