共查询到20条相似文献,搜索用时 15 毫秒
1.
K. B. Jonsson K. Wiberg S. Ljunghall Ö. Ljunggren 《Calcified tissue international》1996,59(5):366-370
Insulin-like growth factor I (IGF-I) has documented anabolic effects on osteoblasts, whereas its influence on osteoclasts
and on bone resorption is unclear. We have investigated the effects of IGF-I on osteoclast recruitment and bone resorption
in vitro. IGF-I (at and above 1 nM) stimulated the formation of multinucleated tartrate-resistant acid phosphatase positive
cells in murine bone marrow cultures, incubated for 9 days. The number of multinucleated cells increased to 540 ± 160% of
control (mean ± SEM) in cultures treated with 10 nM IGF-I. IGF-I (0.1–100 nM) had no effect by itself on 45Ca-release from prelabelled neonatal mouse calvarial bones. However, IGF-I (100 nM) had an inhibitory effect on bone resorption
induced by prostaglandin E2 and 1,25(OH)2D3. These findings indicate that IGF-I enhances the formation of osteoclasts-like cells in long-term bone marrow cultures. In
bone organ cultures, however, IGF-I has an inhibitory effect on stimulated bone resorption, suggesting that IGF-I inhibits
existing osteoclasts and, alternatively, that IGF-I interferes with the osteoblast-derived factor(s) that stimulate existing
osteoclasts.
Received: 15 August 1995 / Accepted: 1 April 1996 相似文献
2.
Alendronate Reduces Adhesion of Human Osteoclast-like Cells to Bone and Bone Protein-Coated Surfaces 总被引:3,自引:0,他引:3
S. Colucci V. Minielli G. Zambonin N. Cirulli G. Mori M. Serra V. Patella A. Zambonin Zallone M. Grano 《Calcified tissue international》1998,63(3):230-235
Bisphosphonates (BPs) are potent inhibitors of bone resorption and are therapeutically effective in disease of increased
bone turnover, but their mechanism(s) of action remain to be elucidated. Using as experimental model human osteoclast-like
cell lines derived from giant cell tumors of bone, extensively characterized for their osteoclast features, we investigated
the adhesive properties of osteoclasts on bone slices and on different proteins of the extracellular matrix in the presence
of BPs. Adhesion assays using bone slices pretreated with ALN, at the established active concentration, showed that, although
the morphology of osteoclasts plated onto pretreated bone slices was not modified, the number of adherent cells was reduced
by the treatment of about 50% vs. controls. The effect of ALN on the adhesion of osteoclast-like cells onto specific extracellular
matrix proteins, such as bone sialoprotein-derived peptide, containing the RGD sequence, conjugated to BSA (BSP-BSA) and fibronectin
(FN), was also tested. In the case of FN the treatment with ALN of protein-coated wells did not modify the percentage of cell
adhesion compared with the control, whereas onto BSP-BSA the presence of ALN significantly reduced adhesion of about 40–45%,
suggesting that the inhibitory effect of ALN on cell adhesion could probably be due to the interference with receptors specifically
recognizing bone matrix proteins as αVβ3 integrins. Furthermore, ALN induced Ca-mediated intracellular signals in osteoclasts, triggering a 2-fold increase in intracellular
calcium concentration.
Received: 8 August 1997 / Accepted: 27 January 1998 相似文献
3.
Human Osteoclast Formation from Blood Monocytes, Peritoneal Macrophages, and Bone Marrow Cells 总被引:6,自引:0,他引:6
J. M. W. Quinn S. Neale Y. Fujikawa J. O. D. McGee N. A. Athanasou 《Calcified tissue international》1998,62(6):527-531
Mononuclear precursors of the human osteoclast have been identified in both bone marrow and the circulation in man, but osteoclast
membership of the mononuclear phagocyte system (MPS) and its precise cellular ontogeny remain controversial. We isolated human
hematopoietic marrow cells, blood monocytes, and peritoneal macrophages and incubated each of these cell populations with
UMR106 osteoblast-like cells on glass coverslips and dentine slices in both the presence and absence of 1,25 dihydroxyvitamin
D3 (1,25(OH)2D3), macrophage-colony stimulating factor (M-CSF), and dexamethasone. Cells isolated from peripheral blood and peritoneal dialysis
fluid were positive only for monocyte/macrophage markers (CD11a, CD11b, CD14, and HLA-DR) and negative for osteoclast markers
[tartrate-resistant acid phosphatase (TRAP), vitronectin reception (VNR), and calcitonin (CT) receptors and did not form resorption
pits on dentine slices after 24 hours in culture. Similarly marrow cells did not form resorption pits on dentine slices after
24 hours in culture. However, after 14 days in co-culture with UMR106 cells, in the presence of 1,25(OH)2D3 and M-CSF, numerous TRAP, CT receptor, and VNR-positive multinucleated cells capable of extensive lacunar resorption were
formed in co-cultures of all these preparations. The presence of 1,25 (OH)2D3, M-CSF, and UMR106 were absolute requirements for osteoclast differentiation. It is concluded that precursor cells capable
of osteoclast differentiation are present in the marrow compartment, the monocyte fraction of peripheral blood, and in the
macrophage compartment of extraskeletal tissues and that these cells are capable of differentiating into mature functional
osteoclasts. These findings argue in favor of osteoclast membership of the human MPS.
Received: 3 January 1997 / Accepted: 14 November 1997 相似文献
4.
Z. Khalkhali-Ellis P. Collin-Osdoby L. Li M. L. Brandi P. Osdoby 《Calcified tissue international》1997,60(2):187-193
Osteoclast development from hematopoietic bone marrow precursors is associated with the expression of various enzymes, receptors,
adhesion molecules, and other specialized components. Among these is a novel 150 kD superoxide dismutase-related membrane
glycoprotein, originally identified by its reaction with the anti-osteoclast monoclonal antibody 121F. This antigen is uniquely
restricted to osteoclasts in bone, universally present on osteoclasts from multiple species, induced during osteoclast differentiation
in vitro and in ovo, and required at high levels for avian osteoclastic bone pit resorption. Expression of a comparable human antigen was investigated
using human leukemic FLG 29.1 cells capable of differentiating towards an osteoclast-like phenotype. Phorbol ester, 1,25 (OH)2 vitamin D3, and osteoblast-derived soluble factors elicited dose and time-dependent inductions of this antigen as measured by enzyme-linked
immunosorbent assay (ELISA) and immunocytochemical staining, coincident with their display of multiple other osteoclastic
features. Synergistic interactions of these modulators led to further elevations in the ultimate expression levels of this
antigen, although not to the full extent associated with in vivo-formed avian osteoclasts. The potent antiresorptive hormone 17β-estradiol, but not its inactive α isomer, partially suppressed
the phorbol ester-induced elevation of the 121F antibody-reactive antigen in FLG 29.1 cells as it does in avian osteoclast-like
cells. Characterization of the human antigen isolated from FLG 29.1 cells by 121F immunoaffinity purification demonstrated
that this regulated membrane component was synthesized by these human cells, more abundant following their differentiation
into osteoclast-like cells, and similar biochemically and immunologically to the 150 kD integral membrane glycoprotein previously
described from avian osteoclasts. Therefore, this report is the first documentation that human osteoclast-like FLG 29.1 cells
express, in a developmentally regulated fashion, a homolog of the specific 150 kD avian osteoclast surface antigen that is
related to superoxide dismutase, a protective free radical scavenging enzyme and is essential for osteoclastic bone resorption.
Received: 1 April 1996 / Accepted: 19 July 1996 相似文献
5.
Several studies have suggested that devitalized bone is less satisfactory than live tissue for surgical grafting purposes
because an initial resorption step, prior to new formation, is lacking. We have compared the osteoclastic resorption of cultured
bone containing living osteocytes with that of similar bone in which the osteocytes were dead. In experiment I, transverse
slices cut from freshly harvested adult rabbit femora were either placed in phosphate buffered saline (Set 1) or subjected
to freezing and thawing (Set 2). In experiment II, a heated set (Set 3) was prepared in addition. All slices were cultured
with osteoclasts for 24 hours, eight slices per set being seeded with bone cells in experiment I and three per set in experiment
II. The areas and volumes of resorption pits formed during the culture period were measured using reflection confocal microscopy.
In both experiments, the mean values for the areas of the pits were smaller in the bone containing live osteocytes (P < 0.03, Mann Whitney test), and in experiment II the volumes of the pits in Set 1 were smaller than those in Set 3 (P < 0.0001, Mann Whitney test). However, in neither experiment was there a significant difference between the Sets in the volume:area
ratios (mean depths) of the pits. The findings show that devitalized bone is resorbed by osteoclasts at least as readily as
bone containing vital osteocytes in vitro, and indicate that if grafted devitalized bone resorbs less well in vivo it is not because the bone tissue is intrinsically resistant to osteoclastic resorption.
Received: 25 November 1997 / Accepted: 24 June 1998 相似文献
6.
When mouse parietal bones were incubated for 1 day in medium containing indomethacin (Ind), the number of tartrate-resistant
acid phosphatase-positive osteoclasts (TRAP+OC) counted on the bone surface was drastically reduced. This reduction did not
occur with calcitonin or if the endocranial membrane (periosteum) was removed prior to incubation with Ind. The aim of this
work was to determine the mechanism involved. TRAP+OC were found to be increased on the endocranial membrane adjacent to the
resorbing surface after Ind treatment, compared with cultures supplemented with parathyroid hormone (PTH) or prostaglandin
E2 (PGE2). However, this increase accounted for only half of those lost from the bone surface. TRAP negative osteoclasts were
also seen on the membrane and, to a lesser extent, on the bone. Increased TRAP specific activity could be extracted from the
endocranial membranes of bones incubated with Ind compared with PGE2 controls. When bones that had been exposed to Ind were
then cultured for 1 day in PGE2, an increase in TRAP+OC occurred. This increase was blocked by the removal of the endocranial
membrane prior to incubation with PGE2. We conclude that when prostaglandin production ceases, TRAP+OC become less adherent
to bone and more adherent to the endocranial membrane. Stimulators of bone resorption appear to reverse this process.
Received: 1 September 1995 / Accepted: 12 February 1996 相似文献
7.
Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB).
Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant
cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed
to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities
exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis,
bone cell proliferation, and osteoblast–osteoclast coupling, were examined by immunohistochemistry using tissue samples from
15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFβ),
epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was
a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth
factor beta (TGFβ), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the
giant cells of GCTB was significant (P < 0.01) for Il-6, TNFβ, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0.05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, ``osteoclastoma' cells in
the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for
stimulated resorption.
Received: 12 February 1996 / Accepted 31 December 1996 相似文献
8.
The purpose of this study was to clarify the involvement of CD4+ and CD8+ T cells on bone resorption induced by Escherichia coli endotoxin. Two kinds of monoclonal antibodies, anti-CD4 and/or anti-CD8, were employed for the depletion of each or both
T cell subsets. E. coli endotoxin was injected into mouse mesial gingiva of the first molar of the left mandible every 48 hours for up to 14 days
(7 injections). The mice were divided into four groups: CD4-depleted, CD8-depleted, T cell-depleted, and normal. The mice
were sacrificed on the day after the 1st, 3rd, 4th, 5th, and 7th injection and alveolar bone was examined histopathologically
and histomorphometrically. Bone surface in contact with osteoclasts was defined as the site of active resorption and the ratios
of active resorption were compared among the four groups. In addition, sections obtained after the 1st, 4th, and 7th injection
were immunohistologically stained in order to confirm the presence or absence of CD4+ or CD8+ T cells. Alveolar bone resorption gradually increased in normal mice as the number of injections increased. In contrast,
alveolar bone resorption was significantly weaker in each or both subset-depleted mice. For the duration of the experimental
period, the number of CD4+ T cells in CD8-depleted and normal mice significantly increased with increasing bone resorption. Considering the function
of CD4+ and CD8+ T cells, these results suggest that each subset preferentially acts as a macrophage activator in the early period of bone
resorption induced by E. coli endotoxin.
Received: 30 May 1997 / Accepted: 14 November 1997 相似文献
9.
Mano M Arakawa T Mano H Nakagawa M Kaneda T Kaneko H Yamada T Miyata K Kiyomura H Kumegawa M Hakeda Y 《Calcified tissue international》2000,67(1):85-92
Prostaglandins (PGs) are well known to be important local factors in regulating bone formation and resorption. PGE2 is a potent stimulator of bone resorption because of enhancing osteoclast formation by its indirect action through stromal
cells. However, the direct action of PGE2 on functionally mature osteoclasts is still controversial. In this study using highly purified rabbit mature osteoclasts,
we examined the direct effect of PGE2 on osteoclastic bone-resorbing activity and its mechanism. PGE2 inhibited resorption pit formation on a dentine slice by the purified osteoclasts in a dose- and time-dependent manner. The
inhibitory effect appeared as early as 4 hours after the PGE2 addition. Forskolin and 12-0-tetradecanoyl phorbol-13-acetate (TPA), respective activators of adenylate cyclase and protein
kinase C, also decreased the osteoclastic bone-resorbing activity. PGE2 increased the content of intracellular cAMP in a dose range effective for the inhibition of bone resorption, whereas the
prostanoid did not alter the intracellular level of inositol triphosphate. The inhibition of osteoclastic bone resorption
by PGE2 was amplified and diminished by a cAMP phosphodiesterase inhibitor (isobutyl methylxanthine) and a protein kinase A inhibitor
(Rp-cAMP), respectively. Of four different subtypes of PGE2 receptors (EPs), EP4 mRNA was predominantly expressed in isolated osteoclasts, whereas the other types of EP mRNA were detected
in only small amounts. These results suggest that the PGE2 inhibitory effect was mediated by an adenylate cyclase system coupled with EP4. This possible association of PGE2 with EP4 in mature osteoclasts was supported by the finding that a specific agonist of EP4 (AE-604) inhibited the bone-resorbing
activity and elevated the intracellular cAMP content. However, butaprost, a selective EP2 agonist, also mimicked the PGE2 effects on isolated osteoclasts although EP2 mRNA expression was minimal. In conclusion, PGE2 directly inhibits bone-resorbing activity of functionally mature osteoclasts by activation of the adenylate cyclase system,
perhaps mainly through EP4.
Received: 21 July 1999 / Accepted: 31 January 2000 相似文献
10.
M. A. Flynn M. Qiao C. Garcia M. Dallas L. F. Bonewald 《Calcified tissue international》1999,64(2):154-159
Leukotriene B4 (LTB4) is elevated in inflammatory conditions and appears to be a potential mediator of inflammation. We have recently shown that
this 5-lipoxygenase metabolite of arachidonic acid stimulates bone resorption in vitro and in vivo. In order to determine the mechanism whereby LTB4 causes bone resorption, avian osteoclasts were examined for the effects of LTB4 and for the presence of LTB4 receptors. Isolated avian osteoclast mononuclear precursor cells, which fuse in culture to form multinucleated cells, were
chosen for receptor binding studies because this population is a morphologically similar source of osteoclasts, and large
numbers of these cells can be obtained from egg-laying hens. Binding of LTB4 and activation would support the hypothesis of a direct effect of this compound on osteoclasts. LTB4 stimulated isolated avian osteoclasts to form resorption lacunae on calcified matrices and to increase their content of tartrate-resistant
acid phosphatase (TRAP), a marker of activated osteoclasts. Receptor binding studies were performed at day 1, when the cells
were mononuclear, at day 4, when mononuclear precursors were actively fusing, and at day 7, when fusion has slowed. Scatchard
analysis of saturation binding data showed two classes of binding sites, a high- and low-affinity binding site with dissociation
constants (KD) of 0.2–0.4 nM and 5.6–24 nM. Association studies showed rapid binding of LTB4 to the cells within 10 minutes. These data show that LTB4 accelerates fusion and activates highly enriched populations of avian osteoclasts and that LTB4 receptors are present in this cell population.
Received: 30 November 1997 / Accepted: 12 May 1998 相似文献
11.
In this study we used an in vitro assay system with osteoblast and osteoclast co-cultures to assess the effect of purified recombinant Pasteurella multocida toxin on bone resorption. Resorption was measured by the release of a telopeptide breakdown product of type I collagen. It
was found that P. multocida did not stimulate bone resorption by osteoclasts directly and also did not stimulate bone breakdown via the release of collagenase
or other proteases from osteoblasts. During co-culture of osteoblasts and osteoclasts, with cell-cell contact prevented, P. multocida toxin produced no significant effect. Osteoblast-conditioned media gave a biphasic effect; low concentrations of P. multocida toxin stimulated bone resorption, whereas 100 ng/ml inhibited resorption by osteoclasts. However, when both cell types were
co-cultured with cell-cell contact permitted, P. multocida toxin induced a large concentration-dependent increase in bone resorption over a 7-day period. This suggested that P. multocida toxin causes bone breakdown via an osteoblast-dependent mechanism and that a membrane-bound receptor may be involved.
Received: 8 July 1997 / Accepted: 8 April 1998 相似文献
12.
Etidronate (EHDP) Inhibits Osteoclastic-Bone Resorption, Promotes Apoptosis and Disrupts Actin Rings in Isolate-Mature Osteoclasts 总被引:2,自引:0,他引:2
Hiroi-Furuya E Kameda T Hiura K Mano H Miyazawa K Nakamaru Y Watanabe-Mano M Okuda N Shimada J Yamamoto Y Hakeda Y Kumegawa M 《Calcified tissue international》1999,64(3):219-223
Bisphosphonates, therapeutic reagents against tumoral bone diseases (Paget's disease or osteoporosis), are potent inhibitors
of bone resorption. The mechanisms by which they directly act on mature osteoclasts remain unclear. Using a recently developed
technique for isolation of highly purified mammalian mature osteoclasts, we demonstrated that etidronate [ethane-1-hydroxy-1,1-diphosphonate
(EHDP), 1-hydroxy-1,1-ethylidenebisphosphonate], inhibited directly osteoclastic bone-resorbing activity by pit assay. In
addition, EHDP also directly induced apoptosis and disrupted actin rings in osteoclasts. The data support previous data on
non-purified osteoclasts and results in vivo.
Received: 26 June 1997 / Accepted: 27 July 1998 相似文献
13.
Summary Bisphosphonates are nonbiodegradable pyrophosphate analogues that are being used increasingly to inhibit bone resorption in
disorders characterized by excessive bone loss. We have previously found that dichloromethylene bisphosphonate (Cl2MBP) inhibits bone resorption through injury to the cells that resorb Cl2MBP-contaminated surfaces. 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) is a more potent inhibitor of bone resorptionin vivo, and we have attempted to identify a step in the resorptive pathway that accounts for this increased potency. We found that
when osteoclasts, isolated from neonatal rat long bones, were incubated on bone slices in the presence of bisphosphonates,
AHPrBP was less, rather than more potent as a resorption-inhibitor than Cl2MBP. The greater sensitivity of resorption to AHPrBPin vivo could neither be attributed to an effect of AHPrBP on the ability of osteoblastic cells to stimulate resorption in response
to calcium-regulating hormonesin vitro nor to an effect on osteoclast generation: osteoclast formation was unaffected by concentrations of AHPrBP 10-fold higher
than those of Cl2MBP which inhibit bone resorption in the bone slice assay. We also found no evidence for impaired osteoclast generationin vivo in AHPrBP-treated rats. These results suggest that the comparisons of potencyin vitro do not include all the factors responsible for determining bisphosphonate potencyin vivo. Because bisphosphonates owe the specificity of their actions to their ability to bind to bone surfaces, we performed experiments
using bone slices that had been immersed in bisphosphonates before use. Bone resorption was virtually abolished on bone slices
preincubated in 10−3 M AHPrBP. Inhibition was associated with degenerative changes in osteoclasts and a more rapid decrease in the number remaining
on the bone surface than occurred with Cl2MBP. The effect was specific for osteoclasts, could be prevented if bone resorption was suppressed by calcitonin, and was
not seen in osteoclasts incubated in AHPrBP on plastic coverslips. These observations suggest that AHPrBP inhibits bone resorption
through injury to osteoclasts when they solubilize bisphosphonate-contaminated bone. We found that the concentration of AHPrBP
used in the preincubation phase could be reduced by an order of magnitude if the volume of the AHPrBP solution was correspondingly
increased. This implies that the concentration of bisphosphonate is less relevant to potency comparisons than the density
of bisphosphonate on the bone surface. The latter will be strongly influencedin vivo not only by affinity for bone but by the pharmacokinetic and other properties of the compound. 相似文献
14.
15.
Nordahl J Hollberg K Mengarelli-Widholm S Andersson G Reinholt FP 《Calcified tissue international》2000,67(5):400-407
Focusing on resorption processes, we have extended our previous studies on chondroclasts and osteoclasts in normally developing
tissues, using a model of nutritionally induced vitamin D-deficiency rickets. To analyze the resorption process, we investigated
the matrix-resorbing cells in this modified and poorly mineralized tissue regarding morphological features and expression
of tartrate-resistant acid phosphatase (TRAP) at the subcellular level. Our goal was to test the hypotheses that initiation
of resorption is impaired with unmineralized matrix, and that such alterations involve changes in the subcellullar distribution
of TRAP, implicating a role for this enzyme in the resorption process. Our results reveal distinctly different morphological
appearances of clast-like cells in rickets compared with normal osteoclasts and chondroclasts. Ordinary resorption structures
of osteoclasts and chondroclasts at the cell-matrix border, i.e., ruffled borders and clear zones, are profoundly altered
in favor of a less well-defined intermediate zone. TRAP distribution at the subcellullar level is also clearly different from
that in osteoclasts and chondroclasts from normal rodents, with impaired secretion; consequently, the enzyme is unable to
function in the matrix outside the ruffled border. Our ultrastructural observations demonstrate that in rickets, the clasts
are incapable of degrading the poorly mineralized cartilage and bone efficiently. Rachitic clasts seem to be recruited to
the matrix surface and interaction between cell and matrix is also initiated, but definitive resorption structures at the
cell-matrix border are not normally developed. Whether resorption is inhibited by the mere lack of mineral or mineral-associated
proteins, or by other mechanisms remains to be settled.
Received: 5 January 2000 / Accepted: 12 May 2000 / Online publication: 2 November 2000 相似文献
16.
After the menopause it has been noted that heavier women conserve bone better than those with lower body weight. The protective
effect of obesity on bone mass has been ascribed to a high body fat content. The present study of 54 postmenopausal women
was undertaken to determine whether circulating plasma levels of leptin, the newly described hormone produced in adipocytes,
were correlated with age-adjusted total body bone mineral content (BMC) or bone mineral density (BMD), or with dynamic biochemical
markers of bone resorption or of bone formation. Leptin values were strongly correlated with all measures of adiposity (P < 0.001). Age-adjusted values for BMC and BMD, respectively, were also positively correlated (P < 0.001) with body weight (r = 0.643, r = 0.502), total fat mass (r = 0.557, r = 0.510) and with plasma leptin concentrations
(r = 0.480, r = 0.551), confirming a positive relationship between fat mass and bone mass. By contrast, no significant correlations
were observed between plasma leptin and dynamic markers of bone resorption (urinary deoxypyridinoline/creatinine r =−0.105,
hydroxyproline/creatinine r =−0.193) or formation (plasma osteocalcin r = 0.103). Because there was no evidence for an association
between ciculating plasma levels of leptin and biochemical markers of either osteoclastic or osteoblastic activity we conclude
it is unlikely that circulating leptin plays any significant direct role in controlling bone cell activity. Our results do
not support the hypothesis that leptin mediates the bone-sparing effects of obesity.
Received: 23 September 1997 / Accepted: 11 May 1998 相似文献
17.
S. Nishida N. Okimoto Y. Okazaki A. Yamaguchi M. Kumegawa K. Yasukawa K. Murayama T. Nakamura 《Calcified tissue international》1998,62(3):227-236
We examined the effects of a monocolonal anti-human gp130 antibody (GPX7), which is known to inhibit interleukin-6 (IL-6)
and leukemia inhibitory factor-mediated responses in human cells on the bone metabolism in normal and ovariectomized (OVX),
7-month-old, Wistar rats for 8 weeks. After confirming the cross-reactivity of the antibody in suppressing the IL-6-mediated
proliferation of rat liver cells, GPX7 was injected once a week at doses of 1 (low dose) or 4 (high dose) mg/kg body weight
(BW). In the lumbar body, bone mineral density values and the trabecular bone volume (BV/TV) were maintained in the GPX7 groups.
The values of the trabecular osteoclast surface and number in the GPX7 high-dose group were significantly smaller than those
in the OVX controls. The double-labeled surface and bone formation rates in the GPX7 high-dose group were significantly increased.
In the proximal tibia, however, the bone mineral content and BV/TV values in the GPX7 groups were smaller, but the trabecular
thickness value in the GPX7 high-dose group was larger than in the OVX control. The single-labeled surface in the GPX7 high-dose
group was significantly larger than that in the OVX control rats. Though the parameter values of trabecular osteoclasts were
apparently smaller, the differences were not significant. 17-β estradiol (0.125 mg/kg BW a week) administration prevented
the bone loss by reducing the parameters of bone formation and resorption in both the lumbar and the proximal tibia. The antibody
administration to the normal rats did not cause any significant changes in the parameters of bone mass and turnover. These
data demonstrate that while GPX7 modulates the bone turnover after ovariectomy in rats, it does not compensate for the action
of estrogen after ovariectomy in rats.
Received: 20 December 1996 / Accepted: 7 August 1997 相似文献
18.
S. Sairanen R. Tähtelä K. Laitinen E. Löyttyniemi M. J. Välimäki 《Calcified tissue international》1997,60(2):160-163
The goal of the present study was to answer the question whether the diurnal variation of markers of bone turnover is abolished
by inhibition of osteoclasts by bisphosphonates and to assess the effects of short-term treatment with clodronate on parameters
of calcium and bone metabolism. Nine healthy, postmenopausal women, all aged 68 years, were studied before and after oral
administration of clodronate, first 800 mg daily for 2 weeks and then 1600 mg daily for 2 weeks. During the two-study sessions
of 24 hours, the subjects received exactly similar meals and were recumbent from 10:00 p.m. to 6:00 a.m. Blood was sampled every 2 hours and urine was collected in 4-hour aliquots. On each study occasion, three markers of bone
resorption (ICTP, serum type-I collagen carboxyterminal telopeptide; F-Pyr, urinary-free pyridinoline; and NTx, crosslinked N-telopeptide of type I collagen) and one marker of bone formation (PICP, serum type I procollagen carboxyterminal
propeptide) showed a diurnal variation; only that of NTx was lessened by treatment with clodronate. Mean area under curve (AUC) values for the 24-hour study periods decreased by
41% (P= 0.0002) and 4.7% (P= 0.016) for urinary NTx and F-Pyr, but remained unchanged for serum ICTP (P= 0.41) and PICP (P= 0.99). Treatment with clodronate decreased mean AUC for the serum concentration of total calcium by 1.4% (P= 0.030) and that for the urinary excretion of calcium by 33% (P= 0.021). Mean AUC for serum-intact PTH increased by 19% (P= 0.004). We conclude that short-term treatment with clodronate lowers serum and urine calcium levels and causes compensatory
hyperparathyroidism. Treatment also clearly decreases the urinary excretion of NTx and lessens its diurnal variation. As assessed by sensitive markers such as NTx, the nocturnal rise in bone resorption is greatly blunted by inhibition of osteoclasts with bisphosphonates.
Received: 13 October 1995 / Accepted: 3 May 1996 相似文献
19.
J. M. W. Quinn A. Sabokbar M. Denne M. -C. de Vernejoul J. O. D. McGee N. A. Athanasou 《Calcified tissue international》1997,60(1):63-70
The effect of prostaglandins (PGs) on osteoclast differentiation, an important point of control for bone resorption, is poorly
understood. After an initial differentiation phase that lasts at least 4 days, murine monocytes, cocultured with UMR106 osteoblastic
cells (in the presence of 1,25-dihydroxyvitamin D3) give rise to tartrate-resistant acid phosphatase (TRAP) positive osteoclast-like cells that are capable of lacunar bone
resorption. PGE2 strongly inhibits TRAP expression and bone resorption in these cocultures. To examine further the cellular mechanisms associated
with this inhibitory effect, we added PGE2 to monocyte/UMR106 cocultures at specific times before, during, and after this initial 4-day differentiation period. To determine
whether this PGE2 inhibition was dependent on the type of stromal cell supporting osteoclast differentiation, we also added PGE2 to cocultures of monocytes with ST2 preadipocytic cells.
Inhibition of bone resorption was greatly reduced when the addition of PGE2 to monocyte/UMR106 cocultures was delayed until the fourth day of incubation; when delayed until the seventh day, inhibition
did not occur. PGE2 inhibition of bone resorption was concentration-dependent and at 10−6 M was also mediated by PGE1 and PGF2α. In contrast to its effects on monocyte/UMR106 cocultures, PGE2 stimulated bone resorption in monocyte/ST2 cocultures. Both ST2 cells and UMR106 cells were shown to express functional receptors
for PGE2.
These results show that PGs strongly influence the differentiation of osteoclast precursors and that this effect is dependent
not only on the type and dose of PG administered, but also on the nature of the bone-derived stromal cell supporting this
process.
Received: 12 October 1995 / Accepted: 1 April 1996 相似文献
20.
The abundance of endothelial cells in bone marrow and the proximity of these cells to osteoclasts and osteoblasts suggest
a role for endothelin-1 (ET-1) on bone metabolism. In vitro, the direct contact with bone endothelial cells induces osteoclastic progenitors to differentiate into mature elements. Recently
it has been reported that ET-1 inhibits osteoclastic bone resorption and cell mobility through a specific receptor on osteoclasts;
other authors demonstrated that ET-1 exerts a mitogenic activity on osteoblast-like cells (MC3T3) by stimulating tyrosin phosphorylation.
We measured ET-1 circulating levels in patients with active Paget's bone disease, a condition with accelerated bone turnover.
For the study we recruited 11 patients with Paget's bone disease (5F, 6M; mean age 68.2 ± 3.6) in the acute stage of the disease;
10 healthy subjects (7F, 3M; mean age 66.5 ± 3.9) were also enrolled as controls. Plasma ET-1 levels were measured with RIA
kits provided by Nichols Institute. Patients showed significantly (P < 0.01) higher ET-1 circulating levels than controls (6.35 ± 1.9 versus 3.4 ± 1.2 pg/ml) with a positive correlation (r =
0.63; P= 0.038) with serum alkaline phosphatase (ALP), but not with urinary hydroxyproline. The higher levels of ET-1 in our patients
suggest a physiopathological role for this peptide in the disease and, could perhaps represent a new useful marker of Paget's
bone disease activity.
Received: 29 April 1997 / Accepted: 20 February 1998 相似文献