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Biomedical subjects

G Passeri

Publications and source records attributed to G Passeri.

31 records · Page 2Linked to original sources
PubMed1993

Demonstration of estrogen and vitamin D receptors in bone marrow-derived stromal cells: up-regulation of the estrogen receptor by 1,25-dihydroxyvitamin-D3.

We have shown earlier that 17 beta-estradiol inhibits cytokine-induced interleukin-6 (IL-6) production by bone marrow-derived stromal cells as well as osteoblasts, two types of cells with a critical influence on osteoclast development, and that ovariectomy causes an IL-6-mediated up-regulation of osteoclastogenesis in mice. Prompted by this, we have searched here for the presence of estrogen receptors (ERs) in two murine bone marrow-derived stromal cell lines, +/+ LDA11 and MBA 13.2, and the osteoblast-like cell line MC3T3-E1. All three cell lines exhibited high affinity saturable binding for [125I]17 beta-estradiol with a dissociation constant of approximately 10(-10) M and concentration of binding sites of 260 +/- 30, 170 +/- 10, and 90 +/- 10 sites per cell, respectively. In addition, we amplified complementary DNA from the stromal cell lines by polymerase chain reaction using oligonucleotide primers flanking the DNA binding domain of the murine uterine ER. The amplified product showed an identical nucleotide sequence to the DNA binding domain of the murine uterine receptor. Consistent with the functionality of the ER in stromal cells, and specifically its role in the regulation of IL-6 by 17 beta-estradiol, we found that the pure estrogen antagonist ICI 164,384 completely prevented the effect of 17 beta-estradiol on IL-6. All three cell lines also expressed receptors for 1,25-dihydroxyvitamin-D3 [1,25(OH)2D3] (dissociation constant, approximately 10(-10) M), with a concentration of binding sites of 490 +/- 20, 920 +/- 20, and 1110 +/- 70 sites per cell, respectively. 1,25(OH)2D3 treatment of the stromal cells caused a 2-fold increase in the concentration of ERs and a decrease in cell proliferation. These data establish that bone marrow-derived stromal cells express functional estrogen as well as vitamin D receptors, which serve to mediate actions of their respective ligands on the biosynthetic activity of these cells and presumably the effects of these two steroid hormones on osteoclastogenesis.

Animals↗
PubMed1993

Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal.

We have previously shown that cytokine-induced production of interleukin-6 (IL-6) by cultured bone marrow-derived stromal and osteoblastic cells is inhibited by 17 beta-estradiol, and that estrogen withdrawal (ovariectomy) in mice causes an up-regulation of osteoclast development which can be prevented by a neutralizing antibody against IL-6 or estrogen replacement. To directly establish the link between estrogen loss and altered IL-6 production, implied by our earlier studies, we have now compared IL-6 production in ex vivo cultures of bone marrow cells from mice that were sham operated, ovariectomized, or ovariectomized and treated with 17 beta-estradiol. In addition, we have examined the effect of the in vitro withdrawal of estrogens from primary cell cultures of neonatal murine calvaria on IL-6 production. IL-6 production in ex vivo cultures of bone marrow cells maintained in the presence of 1,25-dihydroxyvitamin D3 or PTH was greater in marrow cells from ovariectomized mice than in those from sham-operated animals or ovariectomized animals receiving estrogen replacement. In line with this finding, addition of 17 beta-estradiol to calvaria cell cultures followed by withdrawal of the steroid caused an increase in the amount of IL-6 produced in response to the subsequent stimulation of these cultures with IL-1 or PTH compared to that in cultures that had never been treated with estradiol; when the inactive isomer 17 alpha-estradiol was used, no change in IL-6 production was observed. These results establish that estrogen loss causes an up-regulation of IL-6 production by bone marrow cells and that a similar phenomenon can be elicited in vitro by withdrawal of 17 beta-estradiol from primary cultures of bone cells.

Animals↗
PubMed1992

Increased osteoclast development after estrogen loss: mediation by interleukin-6.

Osteoclasts, the cells that resorb bone, develop from hematopoietic precursors of the bone marrow under the control of factors produced in their microenvironment. The cytokine interleukin-6 can promote hematopoiesis and osteoclastogenesis. Interleukin-6 production by bone and marrow stromal cells is suppressed by 17 beta-estradiol in vitro. In mice, estrogen loss (ovariectomy) increased the number of colony-forming units for granulocytes and macrophages, enhanced osteoclast development in ex vivo cultures of marrow, and increased the number of osteoclasts in trabecular bone. These changes were prevented by 17 beta-estradiol or an antibody to interleukin-6. Thus, estrogen loss results in an interleukin-6-mediated stimulation of osteoclastogenesis, which suggests a mechanism for the increased bone resorption in postmenopausal osteoporosis.

Analysis of Variance↗
PubMed1992

Thyroid and other organ-specific autoantibodies in healthy centenarians.

To investigate the prevalence of thyroid autoantibodies in very old subjects, we assayed sera from 34 healthy centenarians (7 men, 27 women; age range 100-108 years) for these antibodies. There was a clear age-dependent increase in prevalence of thyroid autoantibodies in sera from 549 control subjects aged 7-85 years, prevalence in 40 subjects aged 70-85 being significantly greater (p less than 0.001, chi 2) than that in 436 subjects aged less than 50. By contrast, prevalence of thyroid autoantibodies in centenarians was not significantly different from that in controls aged less than 50. Cytofluorimetric analysis of peripheral blood lymphocytes showed a striking age-dependent decrease in total and CD5+B cells (without changes in their ratio), which reached its nadir in centenarians. The age-dependent increase in prevalence of thyroid autoantibodies in the elderly is not seen after the ninth decade of life. What relation this characteristic has to derangement of circulating B cells is unknown.

Adolescent↗
PubMed1992

17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens.

The effect of 17 beta-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Addition of 17 beta-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17 alpha-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17 beta-estradiol. 17 beta-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.

Animals↗
PubMed1991

Histological evidence of increased turnover in bone from spontaneously hypertensive rats.

24 weeks-old spontaneously hypertensive male rats and normotensive genetic controls were subjected to: histomorphometry of the proximal tibiae, assay of mineral density of the femurs by dual photon absorptiometry, and measurement of the calcium content of the femoral bone ash by atomic absorption spectophotometry. Compared with the controls, the hypertensive rats showed osteopenia and increased bone turnover; their osteoid volumes and the surface area of both osteoclasts and osteoblasts were all increased. The data suggest that, during aging, spontaneously hypertensive rats both lose bone mass more rapidly and also have an increased skeletal metabolic rate with respect to the controls.

Animals↗
PubMed1990

Lymphocytes of a patient with lymphoproliferative disease of large granular lymphocytes express high natural killer, ADCC, and LAK activity.

The clinical, morphological, immunological, and molecular features of a case of expansion of large granular lymphocytes (LGL) are reported. Surface marker analysis of peripheral blood and spleen mononuclear cells showed that the majority of these cells were CD3-, CD2+, CD16+, and Leu 7-. Ultrastructural characteristics of CD16+ cells revealed a low nuclear/cytoplasmatic ratio, irregularly shaped nucleus, and numerous cytoplasmatic granules. Functional studies showed reduced proliferative responses to mitogens (PHA, Con A, PWM) and high levels of natural killer (NK) activity as well as antibody-dependent cell cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activities. Molecular analysis of the T cell receptor genes revealed a germline configuration of the beta, gamma, and delta genes; however, as for normal NK cells, delta-related mRNA transcripts were found. Three months from diagnosis, the patient developed profound thrombocytopenia and splenectomy was carried out with complete normalization of the platelet counts and of hematological values while LGL lymphocytosis persisted. Although no tools are available for studying the monoclonality of CD3- lymphoproliferative disease, the clinical course, the absence of chromosomal abnormalities, and a liver histology indicative of chronic active hepatitis suggest that LGL expansion in this patient could be part of a benign, possibly reactive, process.

Adult↗
PubMedDate not supplied

[Bisphosphonates stimulate the production of basic fibroblast growth factor and the formation of bone marrow precursors of osteoblasts. New findings about their mechanism of action].

BACKGROUND: It has been recently shown that bisphosphonates may affect bone resorption either directly on osteoclast activity or through the mediation of osteoblasts activity. In this experimental study the potential effects of etidronate and alendronate on osteoblastic bone formation are investigated. METHODS: The number of fibroblastic colony forming units (CFU-F) and mineralized nodules (CFU-OB) in murine and human bone marrow cultures, assessed. In addition, the basic-FGF production by human osteoblastic cells MG-63 measured. RESULTS: In murine bone marrow cultures etidronate and alendronate stimulate CFU-F formation with a mean increases vs control of 106 +/- 17% at 10(-5) M and 78 +/- 5% at 10(-7) M respectively (p < 0.001). The formation of bone nodules is inhibited by bisphosphonates at high concentrations (> 10(-6) M) and stimulated at lower concentrations (from 10(-7) M to 10(-9) M for etidronate and from 10(-7) M to 10(-10) M for alendronate; p < 0.001). Similarly, in human bone marrow cultures alendronate increases CFU-F formation with a maximal effect at 10(-10) M (+161 +/- 12% vs control; p < 0.01) and the formation of CFU-OB with a maximal effect at 10(-10) M (+133 +/- 34%; p < 0.001). Finally, etidronate (from 10(-9) to 10(-11) M) and alendronate (from 10(-9) to 10(-12) M) stimulate the b-FGF production by human osteoblastic cells (p < 0.01). CONCLUSIONS: In line with previous histomorphometric and clinical observations, the results obtained indicate that bisphosphonates directly affect osteoblastic cells with a positive effect on bone formation, probably via the stimulation of growth factors.

Alendronate↗