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A Taranta

Publications and source records attributed to A Taranta.

At least 19 recordsLinked to original sources
PubMed2001

Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast cytokines.

Malignant melanomas metastasise to the bone and enhance osteoclast bone resorption. We demonstrated that a 48-h-B16 melanoma cell conditioned media (B16CM) induced osteoclastogenesis in mouse bone marrow cultures, without the requirement of B16 cell-bone marrow cell co-culture. B16 cells transcriptionally expressed detectable levels of TGFbeta1, IL-6, M-CSF, GM-CSF and TNFalpha mRNAs, albeit to a lower extent compared with levels in osteoblasts, and failed to express PTHrP, OPGL, OPG and IL-1beta. Interestingly, B16CM greatly upregulated IL-1beta, IL-6 and GM-CSF, and modestly enhanced TNFalpha and OPGL mRNA expression in osteoblasts, suggesting a potential indirect stimulation of osteoclastogenesis via the osteogenic lineage. B16CM barely upregulated c-Fos, but strongly and time-dependently enhanced c-Src expression in the total bone marrow cultures during osteoclast differentiation. Moreover, c-Src expression was enhanced in differentiated and purified osteoclast preparations to higher levels than in stromal cells. In conclusion, melanoma induces osteoclast generation with a paracrine mechanism independent of cell-cell contact, specifically upregulating c-Src in osteoclasts and cytokine expression in osteoblasts.

Animals↗
PubMed2000

Decreased c-Src expression enhances osteoblast differentiation and bone formation.

c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src(-/-) relative to Src(+/+) mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by approximately 60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src(-/-) osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice.

Alkaline Phosphatase↗
PubMed2000

Immediate cell signal induced by laminin in rat sertoli cells.

Rat Sertoli cells in primary culture have been studied for their ability to respond to extracellular matrix macromolecules by increases of [Ca(2+)](i). We observed that cells seeded on glass coverslips, loaded with the intracellular Ca(2+) indicator fura-2, responded to laminin, but not to fibronectin, with an immediate [Ca(2+)](i) raise, with a peak followed by a prolonged plateau. [Ca(2+)](i) increases were dependent upon Ca(2+) influx across the plasma membrane and Ca(2+) release from intracellular Ca(2+) pools. Ca(2+) influx was inhibited by extracellular Ca(2+) removal by EGTA, and by treatment with La(3+), or with the L-type voltage operated Ca(2+) channel blocker, nifedipine. Ca(2+) release from intracellular Ca(2+) storing organelles, was inhibited by the microsomal Ca(2+)-ATPase blocker thapsigargin. Responses were mimicked by synthetic peptides carrying the Arg-Gly-Asp adhesion sequence, but not by the control Arg-Gly-Glu-containing peptide, in which aspartic acid was replaced by glutamic acid. Laminin-dependent [Ca(2+)](i) increases were down-regulated by the follicle-stimulating hormone. However, this occurred only when cells were not subjected to homotypic cell-cell contact, and responded to the hormone with a significant [Ca(2+)](i) elevation. These results indicate that laminin may regulate Sertoli cells by intracellular signals that perturb Ca(2+) homeostasis. This role may be related to an effect exerted by the seminiferous epithelium basement membrane on the regulation of spermatogenesis.

Animals↗
PubMed2000

Transient estrogen exposure of female mice during early development permanently affects osteoclastogenesis in adulthood.

Estrogens modulate bone tissue turnover in both experimental animal models and postmenopausal women. Our previous studies have shown that exposure to diethylstilbestrol (DES) during the perinatal period increases peak bone mass in female mice in adulthood. We investigated whether developmental DES exposure can influence bone mass by affecting osteoclastogenesis. Female mice were injected with 100 microg/kg body weight DES from days 9-16 of gestation or, alternatively, pups received neonatal injections of 2 microg of DES from days 1-5 of life. Animals were weaned at 21 days of age and effects of estrogen on bone cells were evaluated in adulthood. A significant increase in bone mass in female mice was already observed at 2 months, with a maximal effect in older animals. Bone sections from DES-treated animals showed a significant decrease in osteoclast number and tartrate-resistant acid phosphatase (TRAP) enzymatic activity as compared with controls. To verify the importance of the estrogen surge at puberty in this event, a group of control and DES-treated mice were ovariectomized at 17 days to prevent puberty, and potential effect on osteoclastic cells was evaluated in adulthood. As expected, ovariectomy induced an increase of TRAP-positive cells. DES treatment blunted the ovariectomized-dependent increase of the total number of osteoclastic cells, suggesting a role of developmental DES exposure in the process of bone-cell imprinting. Our data indicate, for the first time, that transient changes in estrogen levels during development modulate bone turnover and osteoclastogenesis likely participating in bone-cell imprinting during early phases of bone development, and that this effect could be induced by direct alteration of bone microenvironment.

Animals↗
PubMed1999

Mechanisms of osteoclast dysfunction in human osteopetrosis: abnormal osteoclastogenesis and lack of osteoclast-specific adhesion structures.

Osteoclasts from a patient affected by osteopetrosis were examined in vivo and in vitro. Iliac crest biopsy revealed an osteosclerotic pattern, with prominent numbers of osteoclasts noted for hypernuclearity and incomplete adherence to the bone surface. A population comprising tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated and mononuclear cells, and alkaline phosphatase-positive stromal fibroblasts was obtained in vitro from bone marrow. Mononuclear TRAP-positive precursors spontaneously fused in culture to form giant osteoclast-like cells. These cells expressed the osteoclast marker MMP-9 and calcitonin receptor, and lacked the macrophage marker, Fc receptor. Expression and distribution of c-src, c-fms, and CD68, and response to steroid hormones relevant to osteoclast differentiation and function were apparently normal, whereas cell retraction in response to calcitonin was impaired. TRAP-positive multinucleated cells did not form osteoclast-specific adhesion structures (clear zone, podosomes, or actin rings). Bone resorption rate was severely reduced in vitro. Focal adhesions and stress fibers were observed en lieu of podosomes and actin rings. Adhesion structures contained low levels of immunoreactive vitronectin receptor, most of this integrin being retained in cytoplasmic vesicles. These data provide the first characterization of abnormal differentiation and function of human osteopetrotic osteoclast-like cells.

Acid Phosphatase↗
PubMed1998

Colony stimulating factor-1-induced osteoclast spreading depends on substrate and requires the vitronectin receptor and the c-src proto-oncogene.

The colony stimulating factor 1 (CSF-1) regulates osteoclastogenesis and bone resorption. Mutations in the CSF-1 gene cause an osteopetrosis characterized by the absence of osteoclasts. Mature osteoclasts respond to CSF-1 with inhibition of bone resorption and an increment of cell spreading. Herein we demonstrate that CSF-1-induced osteoclast spreading depends on the substrate the osteoclast interacts with and requires integrity of the vitronectin receptor and of the c-src proto-oncogene. Rabbit osteoclasts were allowed to attach to glass, serum, osteopontin, and bone substrates, and were treated with 10 ng/ml human recombinant CSF-1 for 4 h. In osteoclasts plated on glass, the cytokine induced 70% inhibition of bone resorption and 1.8-fold stimulation of cell spreading, without changes in podosome expression and microfilament array. In contrast, CSF-1 induced a 2.5-fold increase of osteoclasts showing filopodia, and a 9.5-fold increase of osteoclasts presenting lamellipodia, indicating that membrane motility was required for cell spreading. Osteoclasts plated on serum substrates showed a 50% reduction of spontaneous spreading. However, in this circumstance, CSF-1 still stimulated an increase of osteoclast area. In osteoclasts cultured on osteopontin substrate or on bone slices, an inhibition of CSF-1-induced osteoclast spreading was observed. To establish involvement of the vitronectin receptor and c-src proto-oncogene, cells were treated with the alpha vbeta3 integrin neutralizing antibody, LM609, or c-src antisense oligonucleotides, which reduced CSF-1-induced osteoclast spreading by 57% and 60%, respectively. The results demonstrate that CSF-1-induced osteoclast spreading requires both the vitronectin receptor and the c-src proto-oncogene and that this action is modulated by the adhesion substrata.

Actin Cytoskeleton↗
PubMed1997

omega-Conotoxin-sensitive Ca2+ voltage-gated channels modulate protein secretion in cultured rat Sertoli cells.

Recent results have demonstrated that substantial calcium influx in rat Sertoli cells is mediated by cation channels of both L- and N-type. In this report we have investigated the possible role of such channels in the protein secretion of immature rat Sertoli cell monolayers. The blocking of N-type voltage-gated channels by omega-conotoxin (omega-CTX) GVIA results in a 50-60% inhibition of the protein secretion in the culture medium while total protein and RNA synthesis are not affected. The same extent of protein secretion inhibition is obtained in FSH-stimulated Sertoli cells. L-type voltage-gated channels apparently are not involved in such a modulation. These data, showing that a major fraction of secreted proteins from cultured rat Sertoli cells is Ca2+ dependent, represent the first evidence of a physiological role of voltage-operated Ca2+ channels in mammalian testis.

Animals↗
PubMed1996

Growth factor production after polytetrafluoroethylene and vein arterial grafting: an experimental study.

PURPOSE: Occlusion caused by myointimal hyperplasia appears to be the main reason of late failure of polytetrafluoroethylene (PTFE) arterial bypass grafts. Evidence exists that growth factors are involved in the genesis of myointimal hyperplasia. The aim of this study was to assess the release of platelet-derived growth factor (PDGF) and basic fibroblastic growth factor (bFGF) by PTFE arterial grafts. METHODS: In 15 inbred Lewis rats a 1 cm long segment of PTFE was interposed at the level of the abdominal aorta. In a control of another 15 Lewis rats in a vein graft was implanted at the level of the abdominal aorta. Animals were killed four weeks after implantation and the tissue was studied in organ culture for release of PDGF AA, PDGF BB, and bFGF. RESULTS: PTFE grafts released a greater quantity of PDGF AA than did control vein grafts (28 +/- 4 ng/cm2/72 hr vs 7 +/- 2 ng/cm2/72 hr). Similarly, PTFE grafts released a greater quantity of bFGF than did arterial vein grafts (308 +/- 22 ng/cm(2)/72hr vs 204 +/- 20 ng/cm2/72 hr). CONCLUSIONS: We conclude that PTFE arterial grafts released a high quantity of growth factor, which could explain, in part, the occurrence of distal anastomotic myointimal hyperplasia.

Anastomosis, Surgical↗
PubMed1994

Costochondritis. A prospective analysis in an emergency department setting.

BACKGROUND: Costochondritis (CC) is a common, but poorly understood condition among patients with chest wall pain. We have prospectively analyzed distinctive features of patients presenting to the emergency department with chest pain and CC. METHODS: Patients with a chief complaint of chest pain, not due to trauma, fever, or malignancy, were prospectively evaluated for the presence of CC and compared with another chest pain group without CC. RESULTS: Of 122 consecutive patients studied, 36 had CC (30%) and in 17 the pain induced reproduced the original one (15%). Women made up 69% of the patients with CC (vs 31% of control subjects) and Hispanics 47% (vs 24% of control subjects). Only three patients (8%) with CC met the American College of Rheumatology criteria for fibromyalgia, while none of the control subjects did. Widespread pain was more common in the CC group (42% vs 5%). The mean sedimentation rate in the CC group was 44 +/- 31 mm/h vs 41 +/- 31 mm/h in the control group. The acute myocardial infarction rate was 6% in the CC group vs 28% in the control group. Rheumatoid arthritis and osteoarthritis were diagnosed in three and two patients, respectively, of 32 patients with CC cases. One year later, 11 (55%) of 21 patients with CC were still suffering from chest pain, but only one third still had definite CC. CONCLUSIONS: Costochondritis is common among patients with chest pain in an emergency department setting, with a higher frequency among women and Hispanics. It is associated with fibromyalgia in only a minority of cases. Patients with CC appear to have a lower frequency of acute myocardial infarction. Spontaneous resolution is seen in most cases at 1 year.

Aged↗
PubMed1994

Living wills.

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Aged↗
PubMed1994

Improvement in CD4 lymphocyte count in HIV-Reiter's syndrome after treatment with sulfasalazine.

OBJECTIVE: To describe an observed improvement in CD4 lymphocytes in patients with Reiter's syndrome (RS) and human immunodeficiency virus (HIV) infection, after treatment with sulfasalazine (SFSZ). METHODS . Care series. We analyzed CD4 lymphocyte counts in 4 consecutive patients with RS and HIV disease before and after treatment with SFSZ. RESULTS: CD4+ lymphocyte counts increased from a mean of 315 +/- 179 before treatment to 542 +/- 231 x 10(6)/l on followup (p < 0.03), in the absence of antiretroviral therapy. The significance of these observations is discussed. CONCLUSION: Treatment of RS with SFSZ in HIV disease appears to be associated with an improvement in CD4 count.

Adult↗
PubMed1993

Aspirin on trial.

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Acquired Immunodeficiency Syndrome↗
PubMed1992

Thromboxane A2 regulates protein synthesis of cultured human mesangial cells.

Cultured human glomerular mesangial cells express functional receptors for vasoconstrictor metabolites of arachidonate, such as thromboxane A2. Binding of thromboxane A2 analogs triggers phosphatidylinositol breakdown and a rise of intracellular free Ca2+, followed by complex effects on cell growth. We have evaluated the effects of the thromboxane A2 mimetic, U-46619, on the biosynthesis of human mesangial cell proteins. After 4 to 24 hours of incubation with U-46619, cells were metabolically labeled with tritiated leucine or sulfur 35-methionine and analyzed by one-dimensional and two-dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis and fluorography. U-46619 modestly stimulated total protein synthesis in both quiescent and cycling cells to a maximum of 12% and 23% above control at 1 mumol/L after 24 hours, respectively. The eicosanoid selectively enhanced the labeling of crude membrane and cytosolic proteins of molecular weights of approximately 38 to 53 kd and 125 to 200 kd in the presence or absence of serum, respectively. Cellular tubulin and collagen type IV, but not actin, were markedly stimulated, as determined by immunoblotting of cell-associated proteins. On the contrary, U-46619 potently inhibited labeling of soluble proteins that were released into the media, to a maximum of 49% after 24 hours. Inhibition was confirmed by immunoblotting of collagen type IV. Intraglomerular accumulation of thromboxane A2 during chronic inflammation may modify the functional characteristics of the mesangium by regulation of the biosynthesis of structural proteins.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗