INHIBITORY EFFECT OF DIBUTYRYL CYCLIC AMP ON THE RELEASE OF CALCIUM, INORGANIC PHOSPHATE AND LYSOSOMAL ENZYMES FROM CALVARIAL BONES CULTURED FOR 24 HOURS

1979 ◽  
Vol 91 (4) ◽  
pp. 730-742 ◽  
Author(s):  
U. Lerner ◽  
G. T. Gustafson
Keyword(s):  
Bone Resorption ◽  
Culture System ◽  
Inorganic Phosphate ◽  
Lysosomal Enzymes ◽  
Inhibitory Effect ◽  
Bone Culture ◽  
Dibutyryl Cyclic Amp ◽  
The Media ◽  
Old Mice ◽  
Release Processes

ABSTRACT The effect of N6,O2′-dibutyryl adenosine 3′,5′-cyclic-monophosphate (dbcAMP) on the mobilization of calcium (Ca2 +), inorganic phosphate (Pi) and lysosomal enzymes was studied in a bone culture system for 24 h using half calvaria from 6–7 day-old mice. DbcAMP inhibited spontaneous as well as parathyroid hormone-stimulated mineral mobilization. DbcAMP in a concentration of 5 × 10−4m also reduced the activities of β-glucuronidase, β-galactosidase and acid phosphatase found in the media while the activities of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were not affected. It is concluded that cAMP is not a stimulator but an inhibitor of bone resorption within the culture period studied (24 h) and that the cyclic nucleotide might interfere with release processes involved in bone resorption.

scholarly journals Use of forskolin to study the relationship between cyclic AMP formation and bone resorption in vitro

1986 ◽  
Vol 240 (2) ◽  
pp. 529-539 ◽  
Author(s):  
U H Lerner ◽  
B B Fredholm ◽  
M Ransjö
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Cyclic Amp Accumulation ◽  
The Relationship ◽  
Dose Dependent ◽  
Old Mice ◽  
45Ca Release

The effect of the adenylate cyclase activator forskolin on bone resorption and cyclic AMP accumulation was studied in an organ-culture system by using calvarial bones from 6-7-day-old mice. Forskolin caused a rapid and fully reversible increase of cyclic AMP, which was maximal after 20-30 min. The phosphodiesterase inhibitor rolipram (30 mumol/l), enhanced the cyclic AMP response to forskolin (50 mumol/l) from a net cyclic AMP response of 1234 +/- 154 pmol/bone to 2854 +/- 193 pmol/bone (mean +/- S.E.M., n = 4). The cyclic AMP level in bones treated with forskolin (30 mumol/l) was significantly increased after 24 h of culture. Forskolin, at and above 0.3 mumol/l, in the absence and the presence of rolipram (30 mumol/l), caused a dose-dependent cyclic AMP accumulation with an calculated EC50 (concentration producing half-maximal stimulation) value at 8.3 mumol/l. In 24 h cultures forskolin inhibited spontaneous and PTH (parathyroid hormone)-stimulated 45Ca release with calculated IC50 (concentration producing half-maximal inhibition) values at 1.6 and 0.6 mumol/l respectively. Forskolin significantly inhibited the release of 3H from [3H]proline-labelled bones stimulated by PTH (10 nmol/l). The inhibitory effect by forskolin on PTH-stimulated 45Ca release was significant already after 3 h of culture. In 24 h cultures forskolin (3 mumol/l) significantly inhibited 45Ca release also from bones stimulated by prostaglandin E2 (1 mumol/l) and 1 alpha-hydroxycholecalciferol (0.1 mumol/l). The inhibitory effect of forskolin on spontaneous and PTH-stimulated 45Ca release was transient. A dose-dependent stimulation of basal 45Ca release was seen in 120 h cultures, at and above 3 nmol of forskolin/l, with a calculated EC50 value at 16 nmol/l. The stimulatory effect of forskolin (1 mumol/l) could be inhibited by calcitonin (0.1 unit/ml), but was insensitive to indomethacin (1 mumol/l). Forskolin increased the release of 3H from [3H]proline-labelled bones cultured for 120 h and decreased the amount of hydroxyproline in bones after culture. Forskolin inhibited PTH-stimulated release of Ca2+, Pi, beta-glucuronidase and beta-N-acetylglucosaminidase in 24 h cultures. In 120 h cultures forskolin stimulated the basal release of minerals and lysosomal enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

Delayed stimulatory effect of cyclic AMP on bone resorption in vitro

1981 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Ulf Lerner ◽  
Gunnar T. Gustafson
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitors ◽  
Prostaglandin E ◽  
Dibutyryl Cyclic Amp ◽  
Organ Culture System ◽  
Lag Period ◽  
Continuous Presence ◽  
Old Mice

Abstract. The effect of dibutyryl cyclic AMP (dbcAMP) and the phosphodiesterase inhibitors 3-isobutyl methylxanthine (IBMX) and theophylline on bone resorption was studied in an organ culture system for 96– 144 h using half calvaria from 6–7 day old mice. The magnitude of resorption was assessed by measuring the release from the bones of previously incorporated 45Ca. It was observed that dbcAMP, IBMX and theophylline, following a lag period or a period of reduced bone resorption, all progressively increased mineral mobilization. Although the continuous presence of dbcAMP increased mineral mobilization more than a temporary exposure, a limited treatment of 24 h with the nucleotide was sufficient to bring about the delayed stimulatory response. It is concluded that the observations support our earlier proposal that cAMP is not a mediator of the early stages of parathyroid hormone (PTH)- and prostaglandin E2 (PGE2)-stimulated bone resorption. We suggest that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts, a phenomenon which takes more than 24 h to be observed.

Inhibition of bone resorption and lysosomal enzyme release from calvarial bones cultured for 24 hours: synergism between cyclic AMP analogues and phosphodiesterase inhibitors

1980 ◽  
Vol 94 (1) ◽  
pp. 138-144 ◽  
Author(s):  
Ulf Lerner
Keyword(s):  
Bone Resorption ◽  
Lysosomal Enzyme ◽  
Early Stage ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect ◽  
Enzyme Release ◽  
Cyclic Monophosphate ◽  
Pde Inhibitors ◽  
Dose Dependent ◽  
Old Mice

Abstract. The effect of N6-monobutyryl adenosine 3′,5′-cyclic monophosphate (mbcAMP), N6,O2′-dibutyryl adenosine 3′,5′-cyclic monophosphate (dbcAMP), 8-bromo adenosine 3′,5′-cyclic monophosphate (8-brcAMP), adenosine 3′,5′-cyclic monophosphate (cAMP) and two phosphodiesterase (PDE) inhibitors, theophylline and 3-isobutyl-methylxanthine (IBMX) on bone resorption was studied in an organ culture system for 24 h using half calvaria from 6–7 day old mice. The parameters studied were: the release of calcium (Ca2+), inorganic phosphate (Pi), β-glucuronidase, β-galactosidase, lactate dehydrogenase (LDH), and 45Ca from the bones to the medium. With dbcAMP, in concentrations between 5 × 10−5m and 2.5 × 10−4m, and with 8-brcAMP, in concentrations between 10−5m and 5 × 10−5m, a dose-dependent inhibitory effect on the spontaneous release of 45Ca from the explants was found. IBMX and theophylline in doses of 10−3m and 2.5 × 10−3m, respectively, inhibited the spontaneous mobilization of 45Ca, while hypoxanthine, which lacks PDE inhibitory capacity, did not affect the release of 45Ca. When cAMP or its analogues were combined with IBMX, a potentiated inhibitory effect on mineral mobilization and lysosomal enzyme release was seen. In contrast, adenosine 5′-monophosphate, 8-bromo adenosine 5′-monophosphate and sodium butyrate did not reduce the release of 45Ca when applied alone or combined with IBMX. PDE inhibitors combined with parathyroid hormone (PTH) resulted in a reduction of the PTH-stimulated bone resorption. The results provide further evidence that cAMP is not a mediator of the early stage of PTH-induced bone resorption, but on the contrary inhibits mineral mobilization and lysosomal enzyme release from cultured bones.

Inhibitory effect of ipriflavone on osteoclast-mediated bone resorption and new osteoclast formation in long-term cultures of mouse unfractionated bone cells

1993 ◽  
Vol 53 (3) ◽  
pp. 206-209 ◽  
Author(s):  
Kohei Notoya ◽  
Keiji Yoshida ◽  
Shigehisa Taketomi ◽  
Iwao Yamazaki ◽  
Masayoshi Kumegawa
Keyword(s):  
Bone Resorption ◽  
Bone Cells ◽  
Inhibitory Effect ◽  
Osteoclast Formation

scholarly journals Effect of mint (Mentha piperita L.) and caraway (Carum carvi L.) on the growth of some toxigenic aspergillus species and aflatoxin B1 production

2009 ◽  
pp. 131-139 ◽  
Author(s):  
Marija Skrinjar ◽  
Anamarija Mandic ◽  
Aleksandra Misan ◽  
Marijana Sakac ◽  
Ljubisa Saric ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
Dry Weight ◽  
Inhibitory Effect ◽  
Aspergillus Species ◽  
Mentha Piperita ◽  
Ph Values ◽  
Carum Carvi ◽  
The Media ◽  
Total Dry Weight ◽  
Poor Concentration

An inhibitory effect of various concentrations (0.0, 0.5, 1.0, 1.5 and 2,0%) of mint (Mentha piperita L.) and caraway (Carvum carvi L.) on the growth of A. fumigatus, A. flavus and A. ochraceus was examined during 10 days of cultivation in YES medium at temperature of 25?C. Mint showed stronger inhibitory effect than caraway. Total dry weight (g/l) after 10 days of the growth of A. fumigatus in YES medium with 0.5% of mint decreased by about 95%, A. flavus by 97% and A. ochraceus by about 82%. Addition of higher concentrations of mint (1.0, 1.5 and 2.0%) reduced the growth of all tested species. It was poor and hardly visible. pH values of the media increased with the increase of mint concentrations. A. fumigatus showed the highest sensitivity towards caraway and A. flavus the lowest. Total dry weight (g/l) after 10 days of growth of A. fumigatus in medium with 0.5% of caraway decreased by about 72% in comparison to the control. In media with higher concentrations of caraway, its growth was found to be very poor. Concentration of 1.0% of caraway reduced A. flavus growth by 15% and of 1.5% by 92%, in regard to the control. In medium with 2.0% of caraway the growth of A. flavus was observed as poor and hardly visible. The growth of A. ochraceus in medium with 0.5% of caraway decreased by about 85% comparing with control and further decrease was noticed by the increase of concentrations. In medium with 1.5% of caraway a reduction of about 95% of growth was found and under 2.0% of caraway it was poor. pH of the media also increased with the increase of caraway concentrations. Applied concentrations of mint and caraway inhibited completely the production of AB1 by A. flavus.

The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption

2015 ◽  
Vol 6 (10) ◽  
pp. 3351-3358 ◽  
Author(s):  
Wei-Jie Wu ◽  
Min Seuk Kim ◽  
Byung-Yong Ahn
Keyword(s):  
Bone Resorption ◽  
Vitamin K ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect

Vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.

The role of ultimobranchial bodies in the modulation of the response of chick embryos to 1,25-dihydroxycholecalciferol

Development ◽  
1986 ◽  
Vol 97 (1) ◽  
pp. 87-94
Author(s):  
Roberto Narbaitz ◽  
Jaffar Soleimani Rad
Keyword(s):  
Bone Resorption ◽  
Ethyl Alcohol ◽  
Inorganic Phosphate ◽  
Histological Study ◽  
Chorioallantoic Membrane ◽  
Chick Embryos ◽  
Series Of Experiments ◽  
Ultrastructural Characteristics ◽  
Bone Trabeculae

Ultimobranchial bodies (UBBs) were dissected from 17-day-old chick embryos and grafted onto the chorioallantoic membrane of 8-day-old embryos. The embryos with UBB grafts as well as sham-grafted controls were injected on the 10th day of incubation with 100 ng 1,25(OH)2D3 dissolved in ethyl alcohol or with an equal volume of ethyl alcohol alone; embryos were sacrificed on the 13th day. Grafted UBBs showed ultrastructural characteristics typical of actively secreting glands. A histological study of the tibiae from all embryos showed that while the grafted embryos responded to the injection of 1,25(OH)2D3 with a peripheral rim of undermineralized bone trabeculae, sham-grafted embryos never did so. These results confirm the original hypothesis that the presence of differentiated UBBs is a precondition for the production of undermineralized bone (osteoid) by 1,25(OH)2D3. In a second series of experiments, similarly treated embryos were sacrificed on the 10th, 11th, 12th and 13th day; the levels of calcium and inorganic phosphate were determined in their blood. The injection of 1,25(OH)2D3 produced in all embryos hypercalcaemia and hypophosphataemia. However, the hypophosphataemic response was more prolonged in the embryos with UBB grafts than in sham-grafted ones. These results suggest that the grafted UBBs prolonged the hypophosphataemic response, probably by secreting calcitonin and thus reducing the rate of bone resorption. It is also probable that the prolonged hypophosphataemia produced or contributed to the undermineralization of the peripheral (subperiosteal) trabeculae.

scholarly journals Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts

2019 ◽  
Vol 6 (6) ◽  
pp. 190360 ◽  
Author(s):  
Liuliu Yan ◽  
Lulu Lu ◽  
Fangbin Hu ◽  
Dattatrya Shetti ◽  
Kun Wei
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Giant Cells ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
And Function

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40 µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

scholarly journals IMMUNIZATION OF DISSOCIATED SPLEEN CELL CULTURES FROM NORMAL MICE

1967 ◽  
Vol 126 (3) ◽  
pp. 423-442 ◽  
Author(s):  
Robert I. Mishell ◽  
Richard W. Dutton
Keyword(s):  
Spleen Cell ◽  
Cell Cultures ◽  
Culture System ◽  
Cultured Cells ◽  
Inhibitory Effect ◽  
Initial Exposure ◽  
In Vitro Immunization ◽  
In Vitro Response

A culture system for cell suspensions from mouse spleens has been described. The system provides adequate conditions for in vitro immunization on initial exposure to heterologous erythrocytes. The in vitro response closely parallels that observed in vivo with respect to size, early kinetics, antigen dose, and the inhibitory effect of passive antibody. The response of cultured cells differs in two respects from that seen in vivo. There is an increase in the ability to discriminate between different varieties of homologous erythrocytes and the in vitro response does not appear to be limited by whatever mechanisms regulate the in vivo response.

scholarly journals Inhibitory effect of aspirin on bone resorption by active vitamin analogues in vitamin D deficient rats

1979 ◽  
Vol 29 ◽  
pp. 95
Author(s):  
Koichi Ueno ◽  
Minoru Hayashi ◽  
Norio Ohnuma ◽  
Seizi Kurozumi ◽  
Yoshinobu Hashimoto ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Inhibitory Effect ◽  
Active Vitamin
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