Showing papers on "Tartrate-resistant acid phosphatase published in 1994"
TL;DR: It is shown that the partially dephosphorylated proteins no longer support osteoclast binding, indicating that the secretion of TRAP from osteoclasts into the resorption area could exert a regulatory influence on the attachment of the cells to the bone surface.
313 citations
TL;DR: The proposition that human osteoclast-like cells are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts is supported.
Abstract: The decrease in estrogen levels that follows the onset of menopause results in rapid bone loss and osteoporosis. The major effect of estrogen deficiency on bone metabolism is an increase in the rate of bone resorption, but the precise mechanism by which this occurs remains unresolved. A recently developed technique for the isolation of avian osteoclasts has been modified to obtain highly purified multinucleated cells from human giant cell tumors. These osteoclast-like cells have been examined for evidence of estrogen receptors (ERs) and responses to 17 beta-estradiol (17 beta-E2). Analysis of giant-cell RNA demonstrated expression of ER mRNA. Furthermore, immunoblot analysis revealed that the giant cells contained a 66-kDa protein that was recognized by a monoclonal antibody specific for the human ER. When isolated multinucleated cells were cultured on slices of bone, there was a dose-dependent decrease in resorption in response to treatment detectable at 10 pM 17 beta-E2. Treatment with 10 nM 17 alpha-estradiol or vehicle (control) did not inhibit resorption. Moreover, the multinucleated cells isolated from these tumors had decreased mRNA levels for cathepsin B, cathepsin D, and tartrate-resistant acid phosphatase (TRAP) as well as secreted cathepsin B and TRAP enzyme activity in response to treatment with 10 nM 17 beta-E2. In contrast to these data, no change in gene expression was detected in mononuclear cells from these tumors in response to 17 beta-E2 treatment. These data support the proposition that human osteoclasts are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts.
198 citations
TL;DR: In this article, the effect of zinc compounds on osteoclast-like cell formation in mouse marrow culture in vitro was investigated, and it was shown that zinc compounds have a potent inhibitory effect on osteocallastlike multinucleated cells.
172 citations
TL;DR: The recombinant purple phosphatase catalyzed the peroxidation of 5-aminophthalhydrazide (luminol), as evidenced by the induction of chemiluminescence and that ferric iron is essential for enzymatic catalysis, was further indicated by the synergistic effects of the reductant, dithiothreitol, and bipyridyl on phosphat enzyme activity.
145 citations
TL;DR: The expression of some candidate osteoclast markers, tartrate-resistant acid phosphatase (TRAP), macrophage associated antigens (M phi Ag), and vitronectin receptor (VNR) on foreign body giant cells (FBGCs) was investigated in peri-implant tissues of loosened total joint arthroplasties and highlighted the difficulty in distinguishing these two cell lineages.
87 citations
TL;DR: A significant proportion of the peripheral blood mononuclear cells in the monocyte fraction are capable of differentiating into cells showing the cytochemical and functional characteristics of osteoclasts.
Abstract: Osteoclasts are multinucleated cells which form by fusion of circulating mononuclear hemopoietic precursors. The nature of these precursor cells and the roles bone stromal cells and hormonal factors play in their differentiation to osteoclasts are unknown. We cocultured adherent murine blood monocytes (nonspecific esterase and F4/80 positive; tartrate-resistant acid phosphatase negative) with osteoblastic and fibroblastic stromal cell lines in the presence of 2 x 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Tartrate-resistant acid phosphatase and calcitonin (CT) receptor-positive osteoclastic cells, which formed numerous resorption pits in vitro, were noted after only 4 days in coculture with UMR106 osteoblast-like cells. Resorption was seen in cocultures to which as few as 100 peripheral blood mononuclear cells had been added. 1,25-(OH)2D3 and contact with live bone stromal cells were absolute requirements for monocyte differentiation into bone-resorbing cells. Both salmon CT (5 IU/ml) and prostagla...
71 citations
Journal Article•
TL;DR: The high degree of sequence homology indicated that TRAP and PAP enzymes represent a single entity belonging to the class of metalloproteins.
Abstract: Acid phosphatase (AcP, EC 3.1.3.2) is represented by a number of enzymes that can be differentiated according to structural and immunological properties, tissue distribution, subcellular location and other features; these AcP isoenzymes share similar catalytic activity toward phosphoesters in an acidic medium. Classically, AcPs have been divided into four types according to their sensitivity to tartrate and to their origin: erythrocytic, lysosomal, prostatic AcP, and an AcP enzyme that was first identified in hairy cell leukemia (HCL). This latter AcP was termed isoenzyme 5 (based on its electrophoretic mobility) or human type 5, tartrate-resistant acid phosphatase (TRAP). Differences in various physicochemical properties, lack of amino acid sequence similarity and different chromosomal locations of the respective genes showed that the four AcP isoenzymes are not related. The biochemical properties of TRAP are unique: resistance to inhibition by tartrate, but inhibition by molybdate; glycoprotein of 30-40 kDa occurring as two similar isoforms with different carbohydrate content, each composed of dissimilar subunits of 16 and 23 kDa in disulfide linkage; active at acid pH (optimum at 5-6) with basic pI (8.5-9.0); presence of an iron active site giving the purified protein a purple color. The TRAPs of different human sources (HCL spleen, osteoclastoma, Gaucher's spleen, placenta) have an 85-94% homology in their amino acid sequences. Full-length TRAP cDNAs (1.4 kb) have been cloned from human placenta and Gaucher's spleen. Variations in TRAP structure appear to result from post-translational modifications and not from the existence of a multigene family as only a single TRAP gene and a single mRNA species have been reported. This notion of a single TRAP gene is supported by the substantial sequence homology found among the various TRAPs from human tissues and from animal sources (e.g. bovine spleen and bone; rat spleen, bone and epidermis; pig uterus). The latter enzyme preparations of animal origin have been described for many years as the purple acid phosphatase (PAP). However, the high degree of sequence homology indicated that TRAP and PAP enzymes represent a single entity belonging to the class of metalloproteins. The human TRAP gene was assigned to chromosome 15 and to chromosome 19 by two groups. TRAP protein is localized in lysosomes or similar organelles and is not secreted. The serum level of TRAP was found to be increased during physiological bone growth, in Gaucher's disease, and in malignancies metastasized to bone (resulting from increased osteoclastic activity).(ABSTRACT TRUNCATED AT 400 WORDS)
55 citations
TL;DR: Excess expression of TRAP is regulated by iron and that this regulation is exerted at the level of gene transcription, as indicated by transfection experiments which suggest that the 5'-flanking region of the TRAP gene contained iron-responsive elements.
Abstract: Tartrate-resistant acid phosphatase (TRAP) was first identified in cells from patients with hairy cell leukaemia. Subsequently, it has been found in other leukaemias, B-lymphoblastoid cell lines, osteoclasts and subsets of normal lymphocytes, macrophages, and granulocytes. Recent data indicate that TRAP and porcine uteroferrin, a placental iron-transport protein, represent a single gene product. However, the intracellular role of TRAP is unknown. We used a full-length human placental TRAP cDNA probe to examine TRAP expression in human peripheral mononuclear cells (PMCs). TRAP mRNA increased 50-75-fold after 24 h in unstimulated PMC cultures. Cell-fractionation experiments indicated that monocytes were the main cell population accounting for increased TRAP mRNA transcripts, and this was confirmed by histochemical staining for TRAP enzyme activity. Because expression of other iron-binding and -transport proteins is controlled by iron availability, we examined the role of iron in regulating TRAP expression. Increase of TRAP mRNA transcripts in PMCs was inhibited by 50 microM desferrioxamine, a potent iron chelator. The 5' flanking region of the TRAP gene was cloned from a mouse genomic library. In preliminary transient transfection experiments, it was determined that the 5'-flanking region of the TRAP gene contained iron-responsive elements. Therefore, a series of stably transfected HRE H9 cell lines was developed bearing genetic constructs containing various segments of the murine TRAP 5' promoter region driving a luciferase reporter gene. Treatment of transfectants with 100 micrograms/ml iron-saturated human transferrin (FeTF) was performed to assess iron responsiveness of the constructs. Constructs containing a full-length TRAP promoter (comprising base pairs -1846 to +2) responded to FeTF with a 4-5-fold increase of luciferase activity whereas constructs containing only base pairs -363 to +2 of the TRAP promoter did not respond. Constructs containing 1240 or 881 bp of the TRAP promoter gave only a 1.5- to 2-fold increase of luciferase activity with FeTF. In all cases, increase of luciferase activity was blocked by desferrioxamine. Cells transfected with another luciferase construct driven by a simian virus 40 promoter did not show any increase of luciferase activity with FeTF. These data indicate that expression of TRAP is regulated by iron and that this regulation is exerted at the level of gene transcription. The transfection experiments also suggest that the region of the TRAP 5'-flanking sequence between base pairs -1846 and -1240 contains an iron regulatory element.
54 citations
TL;DR: A carboxyl-terminal peptide sequence ('osteostatin') from parathyroid hormone related protein has been shown to have an inhibitory effect on osteoclastic bone resorption as discussed by the authors.
Abstract: A carboxyl-terminal peptide sequence ('osteostatin') from parathyroid hormone related protein has been shown to have an inhibitory effect on osteoclastic bone resorption - an action opposite to its amino-terminal sequence. In this study, we proposed that inhibition of osteoclastic bone resorption by osteostatin was associated with reduction of tartrate resistant acid phosphatase (TRAcP) activity in osteoclasts. Our results have indicated that osteostatin reduced TRAcP activity in a dose dependent manner. This effect of osteostatin was both sensitive (half maximal effect approximately 5 x 10 -13 M) and potent (maximum inhibition approximately 50% of control). In the first 90 min of treatment, however, reduction of TRAcP activity was erratic but became persistent and progressive when the time course was extended. Moreover, throughout the experimental period the levels of TRAcP activity in the culture medium had fallen significantly. It appears that osteostatin has a biphasic effect on TRAcP activity, inhibiting its secretion and either suppressing its synthesis or increasing its degradation. In addition, osteostatin induced rapid cellular retraction of both human and rat cultured osteoclasts, which was morphologically distinct from that produced by calcitonin.
31 citations
TL;DR: Greater than 2 fold increases in tartrate resistant acid phosphatase (TRAP) and bone resorptive activity were observed in the transfected cells compared to controls 3 days after transfection, suggesting that prolonged expression of c-fos caused enhanced osteoclast differentiation.
22 citations
TL;DR: Levels of ICTP in PHPT and secondary HPT have been correlated with those of serum tartrate resistant acid phosphatase (TRAP), another biochemical marker of bone turnover, and with serum levels of intact parathyroid hormone (iPTH), and a significant linear correlation was found.
Abstract: De la Piedra C, Diaz Martin M A, Diaz Diego E M, Lopez Gavilanes E, Gonzalez Parra E, Caramelo C, Rapado A. Serum concentrations of carboxyterminal cross-linked telopeptide of type I collagen (ICTP), serum tartrate resistant acid phosphatase, and serum levels of intact parathyroid hormone in parathyroid hyperfunction. Scand J Clin Lab Invest 1994; 54: 11-15.We have studied the levels of a new biochemical marker of bone resorption, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), in 26 healthy control subjects, 15 patients with primary hyperparathyroidism (PHPT) and 17 patients with secondary hyperparathyroidism (secondary HPT). Levels of ICTP in PHPT and secondary HPT have been correlated with those of serum tartrate resistant acid phosphatase (TRAP), another biochemical marker of bone turnover, and with serum levels of intact parathyroid hormone (iPTH). The ICTP levels of the control group were 2.07 ± 0.58 μgl−1 n = 26, range 1.3-3.2. They were independent of sex and age in the studied...
Journal Article•
TL;DR: The good relation observed between PICP, TRAP and the biochemical indexes of bone activity and iPTH levels suggests the clinical value of these markers in the follow-up of bone involvement in patients with CRF.
Abstract: We have studied the levels of the biochemical markers of bone formation total serum alkaline phosphatase, osteocalcin (BGP) and carboxyterminal propeptide of type I procollagen (PICP), the levels of the biochemical marker of bone resorption serum tartrate-resistant acid phosphatase (TRAP) and those of intact immunoreactive PTH (iPTH) in 30 patients at different stages of chronic renal failure (CRF), all of them without verifiable hepatopathy, and in 9 patients in hemodialysis with hepatopathy measured by the Knodell index Sixteen control subjects were also studied In the group of patients with CRF with or without hepatopathy, the levels of biochemical markers of bone turnover were significantly elevated with respect to those of control patients We did not find any significant difference in the levels of these parameters between the groups with and without liver damage, in spite of the fact that TRAP and PICP are cleared mainly by the liver Levels of TRAP and PICP correlated significantly with the other biochemical markers of bone turnover studied The good relation observed between PICP, TRAP and the biochemical indexes of bone activity and iPTH levels suggests the clinical value of these markers in the follow-up of bone involvement in patients with CRF On the other hand, the frequent hepatopathy found in patients with CRF does not seem to affect to a significant extent the diagnostic value of PICP and TRAP in this pathology
TL;DR: Tartrate-resistant acid phosphatase is an iron-binding protein localized primarily in osteoclasts that may play an important role in the bone resorption process.
TL;DR: Findings indicate that type 5 acid phosphatase, while a cytochemical marker for osteoclasts, can be induced in macrophages by agents that block in vitro osteoclastic differentiation.
Abstract: Type 5 acid phosphatase is a lysosomal enzyme expressed in cells of monocyte/macrophage lineage frequently used as a marker of osteoclastic differentiation. Oligonucleotide primers for DNA amplification were designed following sequence alignment of rat bone and human macrophage type 5 acid phosphatases. DNA (330 bp in length) obtained using these primers and reverse transcribed total cell RNA from in vitro generated murine osteoclastic cells was cloned and sequenced. DNA sequence analysis of two clones demonstrates that the amplified material was 91% and 96% identical to rat bone type 5 acid phosphatase at the nucleotide and amino acid level, respectively. Northern blots of murine tissue RNA show the presence of 1.5-kb transcripts that are most highly expressed in the long bones. Total cell RNA from the osteoclastic cells contain a marked level of type 5 acid phosphatase mRNA when compared to the levels seen in the tissue samples. Additionally, osteoclastic cell RNA contains two additional transcripts of 2.5 and 5 kb. Bone marrow macrophages grown in the presence of M-CSF express low levels of the 1.5-kb transcript with no signal observed for either of the two larger transcripts that were seen in the osteoclastic RNA samples. Importantly, bone marrow macrophage 1.5-kb type 5 acid phosphatase transcript levels are increased by interleukin 4 treatment in both a time and concentration-dependent manner. These findings indicate that type 5 acid phosphatase, while a cytochemical marker for osteoclasts, can be induced in macrophages by agents that block in vitro osteoclastic differentiation. Increased type 5 acid phosphatase may play a role in interleukin 4-stimulated monocyte activities.
TL;DR: It is concluded that TGF-beta 2 is a potent regulator of osteoclastic bone resorption, by modulating both osteoclast migration and osteOClast differentiation.
Abstract: To study the effects of transforming growth factor beta 2 (TGF-beta 2) on bone resorption, cultures of 17-day-old foetal mouse metatarsal long bones were used. The long bone rudiments were cultured for 5 days in medium supplemented with 10% rat serum. The effects of TGF-beta 2 were studied at concentrations of 1, 4, and 10 ng/ml. At all concentrations TGF-beta 2 caused a significant reduction in osteoclastic resorption measured as release of 45Ca from prelabelled bones. The same long bones were subsequently used for histological evaluations. Pre-osteoclasts and osteoclasts were identified as tartrate resistant acid phosphatase (TRAP) positive cells in the mineralized diaphysis, the periosteum around the diaphysis, and the perichondrium around the cartilaginous ends. The distribution of TRAP-positive cells over the three compartments showed that TGF-beta 2 inhibited the migration of TRAP-positive cells from the periosteum into the mineralized diaphysis in a dose dependent manner. In addition, TGF-beta 2 had a biphasic effect on TRAP cell differentiation, as 1 ng/ml increased, but 4 ng/ml and higher decreased TRAP cell numbers. We conclude that TGF-beta 2 is a potent regulator of osteoclastic bone resorption, by modulating both osteoclast migration and osteoclast differentiation.