scholarly journals THE EFFECTS OF PARATHYROID HORMONE, COLCHICINE, AND CALCITONIN ON THE ULTRASTRUCTURE AND THE ACTIVITY OF OSTEOCLASTS IN ORGAN CULTURE

1974 ◽  
Vol 60 (2) ◽  
pp. 346-355 ◽  
Author(s):  
Marijke E. Holtrop ◽  
Lawrence G. Raisz ◽  
Hollis A. Simmons
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Cross Sections ◽  
Clear Zone ◽  
Border Area ◽  
Fetal Rat ◽  
Calcitonin Treatment ◽  
Ruffled Border ◽  
45Ca Release ◽  
Massive Accumulation

The ultrastructure of osteoclasts was examined in fetal rat bones after stimulation or inhibition of resorption in culture. A central ruffled border area completely encircled by a clear zone was considered to represent the resorbing system of the cell. The proportion of ruffled border and clear zone in osteoclast cross sections was compared with changes in bone resorption as measured by the release of previously incorporated radioactive calcium (45Ca). In control cultures 55% of the osteoclast cross sections showed an area closely apposed to bone and this consisted mainly of clear zone; only 11% showed ruffled borders. Treatment with parathyroid hormone (PTH) increased 45Ca release, increased the frequency of finding areas closely apposed to bone (79%), and markedly increased the frequency of the ruffled border area (64%). Colchicine given concurrently with PTH decreased the number of osteoclasts. Colchicine or calcitonin treatment after PTH stimulation decreased the proportion of ruffled border area significantly by 1 h; this was followed by a decrease in 45Ca release. These inhibited osteoclasts resembled osteoclasts from control, unstimulated cultures, suggesting that the cells had returned to their inactive state. Colchicine-treated osteoclasts also showed a loss of microtubules and a massive accumulation of 100 Å filaments, suggesting that synthesis of microtubular subunits had increased.

Effects of ammonium chloride on resorption of fetal rat bones in organ culture

1984 ◽  
Vol 246 (6) ◽  
pp. E516-E518
Author(s):  
A. J. Johannesson ◽  
L. G. Raisz
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Organ Culture ◽  
Ammonium Chloride ◽  
Lysosomal Enzyme ◽  
Potent Inhibitor ◽  
Lysosomal Function ◽  
Fetal Rat ◽  
45Ca Release

Ammonium chloride, a known inhibitor of lysosomal function, was found to be a rapid and potent inhibitor of 45Ca release from fetal rat bones in organ culture. The response to parathyroid hormone and prostaglandin E2 was inhibited in a dose-related, reversible fashion. The activity of the lysosomal enzyme beta-glucuronidase in the medium closely paralleled 45Ca release. Ammonium chloride may now be added to the list of antilysosomal agents that inhibit bone resorption in vitro.

Effects of forskolin on bone in organ culture

1987 ◽  
Vol 252 (1) ◽  
pp. E44-E48
Author(s):  
N. S. Krieger ◽  
P. H. Stern
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Calcium Release ◽  
Dependent Manner ◽  
Bone Culture ◽  
Length Of Treatment ◽  
Fetal Rat ◽  
Neonatal Mouse Calvaria ◽  
Dose Dependent

The effects of forskolin, which directly activates adenylate cyclase in most systems, have been compared with the actions of parathyroid hormone and calcitonin, both of which have been suggested to utilize cAMP as a second messenger in their actions on bone. Forskolin alone stimulated calcium release from neonatal mouse calvaria and fetal rat limb bones in vitro in a dose-dependent manner. The effect was maximal at 10(-6) M in both systems. At higher concentrations forskolin completely inhibited stimulated bone resorption, although with submaximal concentrations the inhibition was only partially sustained up to 72 h. Forskolin directly stimulated cAMP release from calvaria into the medium at concentrations up to 10(-4) M. Forskolin had no effect on the interaction between parathyroid hormone and calcitonin, while calcitonin inhibited the stimulatory effect of forskolin comparably with its inhibition of parathyroid hormone-stimulated bone resorption. The results indicate that forskolin has dual effects on bone and can mimic responses of both parathyroid hormone and calcitonin in both bone culture systems. The observed response depends on the concentration of forskolin used and the length of treatment with the drug.

scholarly journals Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis.

1981 ◽  
Vol 154 (2) ◽  
pp. 529-534 ◽  
Author(s):  
R S Bockman ◽  
M A Repo
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Loss ◽  
Inflammatory Cell ◽  
Prostaglandin Synthesis ◽  
Conditioned Media ◽  
Local Production ◽  
Endogenous Prostaglandin ◽  
Rapid Release ◽  
Fetal Rat

Enhanced synthesis of prostaglandin (PG) E by explanted fetal rat bones was initiated by lymphocyte-conditioned media but not by physiological levels of parathyroid hormone. Rapid release of PGE from bone occurred only when the lymphokine was present. Synthesis of PGE preceded and was necessary for the bone resorption caused by the lymphokine preparation. Local production of prostaglandins in response to inflammatory cell or tumor-derived factors may in part be responsible for the localized bone loss that occurs in certain pathological states.

scholarly journals The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1368-1373 ◽  
Author(s):  
SG Shaughnessy ◽  
E Young ◽  
P Deschamps ◽  
J Hirsh
Keyword(s):  
Molecular Weight ◽  
Bone Resorption ◽  
Unfractionated Heparin ◽  
Dermatan Sulfate ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Rat Calvaria ◽  
Fetal Rat ◽  
45Ca Release ◽  
Calcium Loss

Osteoporosis is a well-recognized complication of long-term heparin use. However, the mechanisms by which heparin can influence bone metabolism are unclear. We report here that unfractionated heparin stimulates the process of bone resorption and that the low molecular weight heparins (LMWHs), enoxaparin, fragmin, logiparin, and ardeparin produce significantly less calcium loss than unfractionated heparin. To assess calcium loss from bone, we quantified the release of 45Ca into the culture medium of fetal rat calvaria. 45Ca release was increased in a dose-dependent manner by the addition of either unfractionated heparin or the LMWHs; but more than 50-fold higher LMWH concentrations were required to obtain an equivalent effect to unfractionated heparin. Thus, at concentration > or = 2 micrograms/mL (0.35 anti-Xa units/mL), unfractionated heparin stimulated 45Ca release 1.53 +/- 0.06 fold. 45Ca release was increased to a similar extent by the addition of either 10(- 7) mol/L parathyroid hormone (PTH) or 10(-6) mol/L 1,25 dihydroxyvitamin D3 (1,25 Vit D3). In contrast to unfractionated heparin, LMWH concentrations > or = 100 micrograms/mL (> or = 14.0 anti- Xa units/mL) were required before maximum isotope release was observed. At concentrations well above therapeutic levels, the LMWHs stimulated 45Ca release by only 1.25 /+- 0.01-fold. Heparins with high and low antithrombin III affinities stimulated 45Ca release equally well. Both size and sulfation were found to be major determinants of heparin's ability to promote isotope release. Thus, the ability of defined heparin fragments to stimulate 45Ca release correlated with their molecular weight, and after N-desulfation the ability of heparin to induce isotope release was greatly diminished. Dermatan sulfate had no effect on 45Ca release. We conclude that size and sulfation are major determinants of heparin's ability to promote bone resorption and that the risk of heparin-induced osteoporosis may be reduced by the use of LMWH preparations.

Inhibition of parathyroid hormone-induced fetal rat bone resorption in vitro by nerve growth factor

1978 ◽  
Vol 26 (1) ◽  
pp. 203-208 ◽  
Author(s):  
Steven L. Teitelbaum ◽  
Roger Y. Andres ◽  
Nancy E. Cooke ◽  
Theodore J. Hahn ◽  
Arnold J. Kahn
Keyword(s):  
Parathyroid Hormone ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Bone Resorption ◽  
Nerve Growth ◽  
Fetal Rat ◽  
Rat Bone

Clear zone in osteoclast function: role of podosomes in regulation of bone-resorbing activity

1991 ◽  
Vol 261 (1) ◽  
pp. C1-C7 ◽  
Author(s):  
A. Teti ◽  
P. C. Marchisio ◽  
A. Z. Zallone
Keyword(s):  
Bone Resorption ◽  
Bone Matrix ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Free Calcium ◽  
Clear Zone ◽  
Discrete Structures ◽  
Free Calcium Concentration ◽  
Ruffled Border ◽  
Osteoclast Function

The adhesion of osteoclasts to the bone matrix is mandatory for bone resorption. Contact of the osteoclast with bone surface induces, in fact, cell polarization and organization of the resorbing apparatus, the so-called “ruffled border.” Cell-matrix interaction in osteoclasts is a complex phenomenon resulting from formation of the “clear zone,” a cytoplasmic area presenting the adhering plasma membrane, or “sealing membrane.” The sealing membrane surrounds the ruffled border and seals the resorbing compartment, namely the extracellular space in which bone resorption takes place. Adhesion at this level occurs via specialized discrete structures, the “podosomes.” Podosomes present most of the protein commonly found in focal adhesions, but with a peculiar organization. They are dynamic elements suitable for regulation, according with the functional demand of the cell. Their assembly increases during bone resorption and is regulated by the cytosolic free calcium concentration and the activity of protein kinase C.

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