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21.
H C Blair S L Teitelbaum H L Tan P H Schlesinger 《Journal of cellular biochemistry》1992,48(4):401-410
Gallium(III) is a new therapeutic agent for hypercalcemia. Ga3+ reduces osteoclast action, but how it inhibits the cell's physiology is unknown. In vivo, 7-12 microM Ga(III) reduces calcium release from bone, but surprisingly, 10-100 microM Ga3+ added to isolated avian osteoclasts did not reduce their degradation of L-(5-3H)-proline bone. 3H-proline labels bone collagen specifically, and collagenolysis is an excellent indicator of bone dissolution because collagen is the least soluble component of bone. Ga(III) greater than 100 microM inhibited osteoclasts in vitro, but also killed the cells. To resolve this apparent conflict, we measured 67Ga distribution between bone, cells, and media. Gallium binds avidly but slowly to bone fragments. One hundred micrograms of bone clears 60% of 1 microM gallium from 500 microliters of tissue culture medium, with steady state at greater than 24 h. Osteoclasts on bone inhibited gallium binding capacity approximately 40%, indicating a difference in available binding area and suggesting that osteoclasts protect their substrate from Ga binding. Less gallium binds to bone in serum-containing medium than in phosphate-buffered saline; 30% reduction of the affinity constant suggests that the serum containing medium competes with bone binding. Consequently, the effect of [Ga] on bone degradation was studied using accurately controlled amounts of Ga(III) pre-bound to the bone. Under these conditions, gallium sensitivity of osteoclasts is striking. At 2 days, 100 micrograms of bone pre-incubated with 1 ml of 1 microM Ga3+, with 10 pmoles Ga3+/micrograms bone, was degraded at 50% the rate of control bone; over 50 pM Ga3+/micrograms bone, resorption was essentially zero. In contrast, pre-treatment of bone with [Ga3+] as high as 15 microM had no significant effect on bone resorption rate beyond 3 days, indicating that gallium below approximately 150 pg/micrograms bone acts for a limited time and does not permanently damage the cells. We conclude that bone-bound Ga(III) from medium concentrations less than 15 microM inhibits osteoclasts reversibly, while irreversible toxicity occurs at solution [Ga3+] greater than 50 microM. 相似文献
22.
The Castel di Guido site, with an estimated age of approximately 300,000 years, has yielded abundant animal remains, Acheulian stone and bone bifaces, and small tools. On the surface of the original deposit, turned over by agricultural activities, fragments of human remains were discovered between 1980 and 1986, including a temporal bone described here. 相似文献
23.
David M. Glassman 《Primates; journal of primatology》1985,26(3):315-324
Intracortical bone remodeling and cortical thickness data were collected from middiaphyseal thin sections of the humerus,
ulna and tibia for 47 specimens ofSaguinus fuscicollis. Individuals were classified into age cohorts: Young Adult, Mid-adult I, Mid-adult II and Old Adult. Correlation analyses
revealed significant relationships between age cohort and the number of osteons for the humerus and ulna, and between age
cohort and non-Haversian canals for each of the three long bone elements. Significant relationships between age cohort and
dimension of cortex size suggested an age-related pattern of cortical shifting in the ulna and older-age bone loss in the
tibia. 相似文献
24.
25.
G C Nicholson S A Livesey J M Moseley T J Martin 《Journal of cellular biochemistry》1986,31(3):229-241
The effects of calcitonin, parathyroid hormone, and prostaglandin E2 on cyclic AMP production were studied in osteoclast-rich cultures derived from medullary bone of laying hens and from the long bones of newborn rats. Cyclic AMP was assayed biochemically in replicate cultures, and furthermore, changes in cytoplasmic fluorescence were sought by indirect immunofluorescence with rabbit anti-cyclic AMP and FITC-labelled goat anti-rabbit IgG. Treatment of rat osteoclasts with calcitonin increased cyclic AMP formation as measured biochemically, and this was confirmed by the immunofluorescence method. No such increase took place in chick osteoclasts. Prostaglandin E2 increased cyclic AMP production in both rat and chick osteoclasts as determined by both methods. Since the immunofluorescence method failed to detect a response to parathyroid hormone either in chick or rat osteoclasts, its variable biochemical effects were concluded to be due to actions on contaminating osteoblasts in the cultures. Thus it has been possible with a combined biochemical and immunocytochemical approach to define the cyclic AMP responses to the calcium-regulating hormones in rat and chick osteoclasts. The failure of calcitonin to increase cyclic AMP in chick osteoclasts identifies a need to investigate the nature of calcitonin action on avian osteoclasts, which may contribute to understanding of its actions on mammalian cells. 相似文献
26.
Although acute alterations in Ca2+ fluxes may mediate the skeletal responses to certain humoral agents, the processes subserving those fluxes are not well understood. We have sought evidence for Ca2+-dependent ATPase activity in isolated osteoblast-like cells maintained in primary culture. Two Ca2+-dependent ATPase components were found in a plasma membrane fraction: a high affinity component (half-saturation constant for Ca2+ of 280 nM, of 13.5 nmol/mg per min) and a low affinity component, which was in reality a divalent cation ATPase, since Mg2+ could replace Ca2+ without loss of activity. The high affinity component exhibited a pH optimum of 7.2 and required Mg2+ for full activity. It was unaffected by potassium or sodium chloride, ouabain or sodium azide, but was inhibited by lanthanum and by the calmodulin antagonist trifluoperazine. This component was prevalent in a subcellular fraction which was also enriched in 5′-nucleotidase and adenylate cyclase activities, suggesting the plasma membrane as its principal location. Osteosarcoma cells, known to resemble osteoblasts in their biological characteristics and responses to bone-seeking hormones, contained similar ATPase activities. Inclusion of purified calmodulin in the assay system caused small non-reproducible increases in the Ca2+-dependent ATPase activity of EGTA-washed membranes. Marked, consistent calmodulin stimulation was demonstrated in membranes exposed previously to trifluoperazine and then washed in trifluoperazine-free buffer. These results indicate the presence of a high affinity, calmodulin-sensitive Ca2+-dependent ATPase in osteoblast-like bone cells. As one determinant of Ca2+ fluxes in bone cells, this enzyme may participate in the hormonal regulation of bone cell function. 相似文献
27.
Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone 总被引:7,自引:0,他引:7
P A Price M R Urist Y Otawara 《Biochemical and biophysical research communications》1983,117(3):765-771
A new protein has been isolated from CaCl2/urea extracts of demineralized bovine bone matrix. This protein has five to six residues of the vitamin K-dependent amino acid, gamma-carboxyglutamic acid (Gla), and we have accordingly designated it matrix Gla protein. Matrix Gla protein is a 15,000 dalton protein whose amino acid composition includes a single disulfide bond. The absence of 4-hydroxyproline in matrix Gla protein demonstrates that it is not a precursor to bone Gla protein, 5,800 dalton protein which has a residue of 4-hydroxyproline at position 9 in its sequence. Matrix Gla protein also does not cross-react with antibodies raised against bone Gla protein. 相似文献
28.
James R. Hummert 《American journal of physical anthropology》1983,62(2):167-176
Cortical bone growth is analyzed for 174 children from a Medieval Christian population at Kulubnarti in the Batn el Hajar of Sudanese Nubia (550–1450 AD ). Using the tibia as a representative long bone, total subperiosteal area, cortical area, medullary area, and percent cortical area at midshaft were calculated. While growth in total and cortical areas, as well as in length, appear to be fairly well maintained, percent cortical area reveals unusual growth patterns which reflect excessive endosteal resorption. Compared to the relative reduction in bone mass which has been observed in malnourished living children, as well as with previously reported evidence for stress in the Kulubnarti population, the present data support an interpretation of nutritionally related stress and of no major diachronic dietary change. 相似文献
29.
Modularity of osteoclast behaviour and “mode-specific” inhibition of osteoclast function 总被引:2,自引:0,他引:2
Mone Zaidi 《Bioscience reports》1990,10(6):547-556
This study is part of an attempt to understand the role of specific cellular activities in the bone resorptive process. Experiments were performed whereby known pharmacological agents were used to inhibit individual modes of osteoclastic activity, such as motility and secretion. The effects of such treatments on bone resorption were assessed by quantitative scanning electron microscopy. The compounds included colchicine, which was used to inhibit osteoclast motility; molybdate ions which were used to selectively inhibit the catalytic activity of secreted acid phosphatase, and omeprazole which was employed to inhibit the secretion of hydrogen ions. All compounds inhibited osteoclastic bone resorption, but singularly affected defined modes of activity. These findings suggest that each mode of osteoclastic activity is essential for the bone resorptive process, and that mode-specific inhibition may provide a means whereby excessive activity of the osteoclast can be regulated in disease. 相似文献
30.
On the mechanical characterization of compact bone structure using the homogenization theory 总被引:1,自引:0,他引:1
In a previous paper (Crolet et al., 1993, J. Biomechanics 26, 677–687), a modelling of the mechanical behavior of compact bone was presented, in which the homogenization theory was the basic tool of computation. In this simulation, approximations were used for the modelling of the lamellae and the osteons: the lamella and the osteon were divided into cylindrical sectors, each sector being approximated as a parallelepiped having a periodic structure (fibrous composite for the lamella, superimposition of plates for the osteon). The present study deals with a new model without these approximations. First, it can be proved that the homogenized elasticity tensor for a lamella, which has a non-periodic structure, is obtained at each geometrical point as a homogenized tensor of a periodic problem. Similarly, for the osteonal structure, the components of the homogenized tensor are determined at each point as the result of a periodic homogenization.
The software OSTEON, which is the computational method associated with this model, allows one to obtain a better understanding of the effects of many bony parameters. The obtained results are in accordance with experimental data. 相似文献