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O Ljunggren

Publications and source records attributed to O Ljunggren.

68 records · Page 4Linked to original sources
PubMed1991

Inhibitory effects of gamma-interferon on bradykinin-induced bone resorption and prostaglandin formation in cultured mouse calvarial bones.

The effects of mouse recombinant gamma-interferon (gamma-IFN) and indomethacin on bone resorption stimulated by bradykinin, Lys-bradykinin, Met-Lys-bradykinin, des-Arg9-bradykinin and prostaglandin E2 (PGE2) have been studied using cultures of neonatal calvarial bones and analyzing the release of 45Ca from prelabelled bones as a parameter of bone resorption. In addition, the effects of gamma-IFN and indomethacin on formation of PGE2 in bone cultures stimulated by bradykinin was analyzed. Indomethacin (1 mumol/l) totally abolished bradykinin (1 mumol/l) induced 45Ca release. The inhibitory effect of indomethacin could be fully reversed by addition of PGE2 (1 mumol/l). gamma-IFN (1000 U/ml) almost totally inhibited 45Ca release stimulated by bradykinin (1 mumol/l), but the inhibitory effect could only be partially overcome by PGE2. gamma-IFN and indomethacin also inhibited the stimulatory effects of Lys-bradykinin, Met-Lys-bradykinin and des-Arg9-bradykinin (1 mumol/l) on 45Ca release. The stimulatory effects of PGE2 (1 mumol/l) on radioactive calcium mobilization was partially inhibited by gamma-IFN (1000 U/ml), whereas indomethacin (1 mumol/l) was without effect. The inhibitory effect of gamma-IFN on 45Ca release stimulated by bradykinin and PGE2 was dose-dependent with threshold for action at 3-30 U/ml. Comparative dose-response curves showed that gamma-IFN was most potent as inhibitor of bradykinin induced 45Ca release. Bradykinin (1 mumol/l) significantly stimulated PGE2 formation by a mechanism that was completely inhibited by indomethacin (1 mumol/l). gamma-IFN (1000 U/ml) partially inhibited the stimulatory effect of bradykinin on PGE2 formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Thrombin increases cytoplasmic Ca2+ and stimulates formation of prostaglandin E2 in the osteoblastic cell line MC3T3-El.

Using microfluorometric analysis in individual, fura-2 loaded cells, we found that thrombin (0.1-10 U/ml) caused a dose-dependent (EC50 approximately 0.5 U/ml), rapid (within seconds), transient increase in cytoplasmic Ca2+ in the osteoblastic cell line MC3T3-El. The thrombin induced rise in cytoplasmic Ca2+ was not dependent on extracellular Ca2+ and was unaffected by indomethacin. In MC3T3-El cells, thrombin (0.3-10 U/ml) caused a rapid and dose-dependent (EC50 approximately 0.5 U/ml) stimulation of PGE2 formation. The calcium ionophore A23187 (2 mumol/l) also rapidly stimulated an increase in cytoplasmic Ca2+ and the formation of PGE2 in MC3T3-El cells. These data indicate that thrombin mobilizes Ca2+ from intracellular stores and that Ca2+ may serve as a second messenger in thrombin induced stimulation of PGE2 biosynthesis in osteoblasts.

Animals↗
PubMed1991

Comparison of human interleukin-1 beta and its 163-171 peptide in bone resorption and the immune response.

Human interleukin-1 beta (IL-1 beta) caused a dose- and time-dependent enhancement of the release of 45Ca from prelabeled mouse calvaria in organ culture. In addition, IL-1 beta dose-dependently stimulated the formation of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha in the calvarial bones. However, IL-1 beta-induced 45Ca release was only partially inhibited by blocking the PGE2 response with indomethacin, suggesting that enhanced PGE2 formation in response to IL-1 beta is not necessary to obtain a bone resorptive effect, but that prostaglandins potentiate the action of IL-1 beta. The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, administered simultaneously with antigen (SRBC) to C3H/HeN male mice, induced a dose-dependent enhancement of specific antibody-producing cells in the spleen (PFC). The degree of PFC stimulation was comparable to that caused by native human IL-1 beta. In mouse bone cultures, neither 45Ca release nor prostanoid formation was stimulated by fragment 163-171. These data indicate that (1) IL-1 beta-induced stimulation of bone resorption is dissociable from IL-1 beta-induced increase of prostanoid biosynthesis and (2) the epitope of the IL-1 beta molecule involved in the immunostimulatory effects may be different from that involved in the stimulatory effects on bone resorption.

Amino Acid Sequence↗
PubMed1991

On the role of polyamines in bone resorption induced by parathyroid hormone.

In order to elucidate the possible role of polyamines in the mobilization of mineral from long-term bone cultures stimulated with parathyroid hormone we have measured the activity of ornithine decarboxylase in osteoblasts, the levels of polyamines in calvarial bone and determined the effect of added polyamines and inhibitors of polyamine biosynthesis on calcium mobilization. Parathyroid hormone (10 nmol l-1) stimulated omithine decarboxylase activity by approximately 50% in both cultured bone cells of osteoblastic phenotype, UMR 106 and in mouse calvarial osteoblast-like cells. In mouse calvaria the levels of putrescine and spermidine were increased by parathyroid hormone after 24 hours. The levels of spermine were very low and were unchanged by parathyroid hormone. The two polyamine synthesis inhibitors alpha-difluoromethylornithine (DFMO; 2 mmol l-1) and methylglyoxal-bis-guanylhydrazone (MGBG; 50 mu mol l-1) did not significantly affect the mobilization of 45Ca from parathyroid hormone-stimulated bones. All three polyamines, putrescine, spermidine and spermine, inhibited the mobilization of 45Ca induced by parathyroid hormone in a dose-dependent manner. The inhibition induced by putrescine was reversible. In summary, we have shown that parathyroid hormone increases the accumulation of polyamines in bone, but the effect is small. Furthermore, inhibition of polyamine biosynthesis does not reduce parathyroid hormone-induced mineral mobilization and the addition of polyamines leads to a reduced rather than a stimulated mineral mobilization. Thus, polyamines do not seem to be critically involved in the changes in bone resorption induced by parathyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Bradykinin stimulates prostaglandin E2 formation in isolated human osteoblast-like cells.

The effect of bradykinin on prostaglandin E2 formation in cells from human trabecular bone has been studied. The cells responded to parathyroid hormone with enhanced cyclic AMP formation and were growing as cuboidal-shaped, osteoblast-like cells. In these isolated human osteoblast-like cells, bradykinin (1 mumol/l) caused a rapid (5 min) stimulation of prostaglandin E2 formation. This finding indicates that human osteoblasts are equipped with receptors for bradykinin linked to an increase in prostaglandin formation.

Bradykinin↗
PubMed1990

Evidence for BK1 bradykinin-receptor-mediated prostaglandin formation in osteoblasts and subsequent enhancement of bone resorption.

1. The effects of the BK1 bradykinin (BK)-receptor agonist des-Arg9-BK on bone resorption and prostaglandin formation in osteoblasts have been studied. 2. Des-Arg9-BK (1 microM) stimulated the release of 45Ca from prelabelled neonatal mouse calvarial bones and the formation of prostaglandin E2 (PGE2) in calvarial bones. The stimulatory effect on bone resorption and PGE2 formation could be totally inhibited by indomethacin, flurbiprofen and hydrocortisone. 3. The BK1 receptor antagonist des-Arg9-Leu8-BK (10 microM) inhibited des-Arg9-BK (0.01-0.1 microM)-induced release of 45Ca from prelabelled neonatal mouse calvarial bones, while leaving BK (0.1-1 microM)-induced 45Ca release unaffected. 4. In isolated osteoblast-like cells from neonatal mouse calvarial bones, des-Arg9-BK (1 microM) induced a slowly developing increase in PGE2 formation that was significantly different from untreated controls after 24 h. Treatment with BK caused a rapid burst (within minutes) of PGE2 formation. 5. Des-Arg9-Leu8-BK (10 microM) selectively inhibited des-Arg9-BK (1 microM)-induced PGE2 and prostacyclin formation in isolated osteoblast-like cells incubated for 72 h. Des-Arg9-Leu8-BK did not affect BK and Lys-BK (1 microM)-induced PGE2 and prostacyclin formation in isolated osteoblast-like cells incubated for 72 h. 6. These data indicate that osteoblasts are equipped with BK1-receptors mediating enhanced prostaglandin formation and subsequent bone resorption.

Animals↗
PubMed1990

Bradykinin-2 receptor-mediated release of 3H-arachidonic acid and formation of prostaglandin E2 in human gingival fibroblasts.

Bradykinin stimulated production of prostaglandin E2 (PGE2) and the release of 3H-arachidonic acid by gingival fibroblasts in a time- and dose-dependent manner. The effect on PGE2 biosynthesis was seen already after 15 seconds and was maximal after 5 minutes. Several structurally unrelated inhibitors of arachidonic acid metabolism via the cyclooxygenase pathway totally abolished the PGE2 response to bradykinin. The stimulation of PGE2 formation was seen at and above 10 nmol/l of bradykinin. Des-Arg9-bradykinin was 100-fold less potent compared to bradykinin. Des-Arg9-Leu8-bradykinin did not antagonize bradykinin-induced PGE2 formation. Met-Lys-bradykinin and Lys-bradykinin also enhanced PGE2 formation in gingival fibroblasts. The stimulatory action of bradykinin on 3H-arachidonic acid release was observed after 30 s and progressively increased for at least 15 min. The stimulatory effect on 3H-arachidonic acid release by bradykinin was seen at and above 10 nmol/l, whereas des-Arg9-bradykinin was without effect up to a concentration of 1 mumol/l. Indomethacin did not affect bradykinin-induced 3H-arachidonic acid release. These data show that bradykinin, via a B2-receptor-mediated pathway, can stimulate arachidonic acid release and subsequent prostanoid formation in gingival fibroblasts. Consequently, gingival fibroblasts may contribute, by a bradykinin-regulated reaction, to the enhanced amounts of prostanoids found in gingival tissues and crevicular fluids in patients with periodontal diseases.

Analysis of Variance↗
PubMed1989

Bradykinin stimulates production of prostaglandin E2 and prostacyclin in murine osteoblasts.

The effect of bradykinin on prostaglandin production in mouse calvarial bones and in isolated osteoblasts has been examined. Bradykinin (1 mumol/l) stimulated prostaglandin formation in neonatal mouse calvarial bones incubated for 30 min. In isolated osteoblast-like cells from neonatal mice calvarial bones and in a cloned mouse calvarial osteoblastic cell lineage (MC3T3-E1) bradykinin stimulated the production of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin). The stimulation of PGE2 production occurred rapidly (30 s) and reached its maximum after 5-10 min. The stimulatory effect of bradykinin on PGE2 production in isolated osteoblast-like cells and in MC3T3-E1 cells was dose dependent with apparent half maximal stimulation seen at 10 and 3 nmol/l, respectively. Bradykinin-induced prostaglandin production was totally reversible after withdrawal of the agonist. Pretreatment with bradykinin (1 mumol/l) resulted in desensitization to a subsequent challenge with bradykinin (1 mumol/l), while pretreatment with bradykinin had no effect upon arachidonic acid (30 mumol/l) induced prostaglandin formation. Bradykinin-induced production of PGE2 was abolished by several structurally unrelated, competitive and non-competitive inhibitors of arachidonic acid metabolism as well as by corticosteroids. The mouse calvarial osteoblast-like cells also showed a PGE2 and 6-keto-PGF1 alpha response to thrombin, but not to parathyroid hormone (PTH), calcitonin and 1 alpha(OH)D3. The formation of cyclic AMP in mouse calvarial osteoblasts was enhanced by PTH, bradykinin, thrombin and arachidonic acid but not by calcitonin and 1 alpha(OH)D3. The cyclic AMP response to bradykinin, thrombin and arachidonic acid, but not that to PTH, was abolished by indomethacin. The degree of confluency of the cell cultures greatly influenced the amount of prostaglandins being produced. At higher cell density the amount of prostanoids synthesized per cell was substantially decreased in untreated control cultures as well as in bradykinin- and arachidonic acid-treated cells. These data suggest that osteoblasts are equipped with receptors for bradykinin coupled to prostaglandin production.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Forskolin sensitizes parathyroid hormone-induced cyclic AMP response, but not the bone resorptive effect, in mouse calvarial bones.

The effect of forskolin on parathyroid hormone (PTH) stimulated bone resorption, as assessed in vitro by the release of 45Ca from prelabelled neonatal mouse calvarial bones, and cyclic AMP formation in mouse calvarial bones and osteoblast-like cells was investigated. Much higher concentrations (100-300-times) of PTH were required to stimulate cyclic AMP accumulation than to stimulate mineral mobilization in murine calvarial bones. PTH, in the absence of phosphodiesterase inhibitor, stimulated cyclic AMP formation in mouse calvarial bones at and above concentrations of 3-10 nmol/l with EC50 at 10-15 nmol/l. In the presence of forskolin (1 or 10 mumol/l) the minimal concentration required to obtain a cyclic AMP response to PTH was decreased by a factor of 30-100 and the EC50 value was decreased to 1-2 nmol/l. Similar results were seen in osteoblast-enriched cells. In addition, the magnitude of the PTH-induced cyclic AMP response was substantially potentiated by forskolin, both in calvarial bones and in isolated osteoblasts. Forskolin, in the absence of PTH, stimulated cyclic AMP levels in mouse calvaria at and above 1 mumol/l. In the presence of PTH, the response to forskolin was potentiated over the whole dose-response curve with apparent EC50 value at 1-2 mumol/l of forskolin. Forskolin (1 mumol/l) did not affect the magnitude of the 45Ca release response to PTH in 24 or 48 h cultures. In 96 h cultures, forskolin, in an additive manner, potentiated the effect of PTH on calcium mobilization. These results show that forskolin, in mouse calvarial bones and in isolated osteoblasts, in addition to directly stimulating cyclic AMP, can enhance receptor-mediated activation of adenylate cyclase. The finding that forskolin did not synergistically potentiate PTH-induced bone resorption suggests that there is no simple relationship between PTH-induced cyclic AMP formation and stimulation of bone resorption.

Animals↗
PubMed1989

Thrombin and bradykinin enhance prostaglandin production in human peripheral blood monocytes.

Thrombin and bradykinin stimulate production of prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin) in isolated human peripheral blood monocytes in a dose- and time-dependent manner. Since PGE2 and prostacyclin can affect the activity of immunocompetent cells and bone resorbing osteoclasts, our finding indicates that thrombin and bradykinin, both of which are formed in inflammatory processes as a consequence of activation of the Hageman factor (coagulation factor XII), may have important roles in the modulation of the inflammatory response and the loss of alveolar bone in periodontitis.

Arachidonic Acids↗
PubMed1989

Parathyroid hormone stimulates prostanoid formation in mouse calvarial bones.

Bovine parathyroid hormone (bPTH 1-34) caused a time- and dose-dependent enhanced formation of the two prostanoids PGE2 and 6-keto-PGF1 alpha in cultured neonatal mouse calvarial bones, with threshold for action at 0.1 nmol/l. The PGE2 response to PTH was completely blocked by indomethacin, but insensitive to calcitonin. By contrast, indomethacin was without effect on 45Ca release induced by PTH. The PTH analogues (Nle 8, 18, Tyr 34)-bPTH (3-34) amide and (Tyr 34)-bPTH (7-34) amide, which are putative PTH antagonists, did not affect basal production of PGE2, nor did the analogues affect bPTH 1-34 induced PGE2 formation. The data show that PTH stimulates prostanoid formation in mouse bone cells and that this response is not directly linked to PTH-induced bone resorption.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Prostaglandin E2 causes a transient inhibition of mineral mobilization, matrix degradation, and lysosomal enzyme release from mouse calvarial bones in vitro.

The effect of prostaglandin E2 (PGE2) on the kinetic of bone resorption in vitro was assessed by following the release of minerals and degradation of matrix in cultured mouse calvarial bones. PGE2 (1 and 3 mumol/liter) caused an initial inhibition of the release of 45Ca, stable calcium, and inorganic phosphate from unstimulated calvarial bones. The effect was transient and after 24 and 48 hours the release of 45Ca, stable calcium, and inorganic phosphate from PGE2-treated bones was enhanced. 0.3 mumol/liter of PGE2 stimulated the release of 45Ca after 24 hours, but at this concentration no initial inhibition was observed. The initial inhibitory effect of PGE2 (1 mumol/liter) could be further increased by three structurally different inhibitors of cyclic AMP breakdown. PGE2 (1 mumol/liter) caused not only an initial inhibition of mineral release but also an initial inhibition of matrix degradation, as assessed by the release of 3H from [3H]-proline labeled bones. In addition, PGE2 (3 mumol/liter), in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, caused a rapid (6 hours) inhibition of the release of the lysosomal enzymes beta-glucuronidase and beta-N-acetyl-glucosaminidase, without affecting the release of the cytosolic enzyme lactate dehydrogenase. Similar specific initial inhibition of lysosomal enzyme release was also seen in the presence of calcitonin and dibutyryl cyclic AMP, but not in the presence of parathyroid hormone (PTH). Neither PGE2 nor the phosphodiesterase inhibitors rolipram and Ro 20.1724, could inhibit the initial stages of PTH-induced 45Ca release. Nor did PGE2 inhibit the stimulation of radioactive calcium mobilization induced by 1 alpha (OH)-vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1986

Stimulation of bone resorption in cultured mouse calvaria by Lys-bradykinin (kallidin), a potential mediator of bone resorption linking anaphylaxis processes to rarefying osteitis.

Lys-Bradykinin (kallidin) stimulated bone resorption in vitro as assessed by the release of 45Ca and 3H from mouse calvaria radiolabelled in vivo with [45Ca]CaCl2 and [3H]proline, respectively. The stimulatory effect of Lys-bradykinin was reduced by calcitonin, indicating that the bone resorptive effect of Lys-bradykinin was dependent on osteoclastic activity. Different inhibitors of arachidonic acid metabolism, including glucocorticoids, inhibited Lys-bradykinin stimulated mobilization of mineral, implicating the synthesis of prostaglandins as an intermediary step. Lys-Bradykinin enhanced the biosynthesis of PGE2 in osteoblast-like cells isolated from mouse calvaria. In view of these findings and the capacity of mast cells to generate kininogenase activity, resulting in formation of Lys-bradykinin and bradykinin, the role of these cells in the pathogenesis of bone loss in rheumatoid arthritis, mastocytosis and osteoporosis is discussed.

Anaphylaxis↗