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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone morphogenetic protein 3 (BMP3) is a potent osteoinductive growth factor belonging to the TGF-beta superfamily. In this study, we engineered a recombinant BMP3 protein to include an auxiliary collagen-targeting domain derived from von Willebrand coagulation factor (vWF). The collagen-targeted BMP3 fusion protein (rhBMP3-C) was expressed in E. coli, purified from bacterial inclusion bodies, renatured under controlled redox conditions, and assayed for biological activity in vitro and in vivo. The renatured rhBMP3-C fusion protein bound tightly to collagen matrices and inhibited DNA synthesis in normal rat calvaria cells and in two out of three human osteosarcoma cell lines tested. Alkaline phosphatase activity was increased in rat calvarial cells and was decreased in osteosarcoma cells in vitro in a dose-dependent manner. Collagen sponges impregnated with rhBMP3-C and implanted subcutaneously in Fischer-344 rats induced dose-dependent dystrophic calcification of the collagen matrix, with no evidence of ectopic bone formation. However, local injection of rhBMP3-C infused in a collagen suspension induced new bone formation on the periosteal surface of rat calvaria. Finally, in a rat cranial defect model, surgical implantation of rhBMP3-C arrayed on either collagen sponges or on porous ceramics coated with Type I collagen exhibited marked osteoinductive properties. Taken together, these results demonstrate the feasibility of engineering and manufacturing targeted-BMPs which exhibit an integral gain-of-function that may be exploited to therapeutic advantage in (i) the enhancement of effective local concentrations, (ii) the prevention of systemic biodistribution and side effects, and (iii) the design of improved osteoinductive matrices.
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PMID:Collagen-targeted BMP3 fusion proteins arrayed on collagen matrices or porous ceramics impregnated with Type I collagen enhance osteogenesis in a rat cranial defect model. 1216 63

To observe the differentiation and gene expression of human osteosarcoma cell line MG-63 in culture. Alkaline phosphatase (ALP) activity was determined by p-nitrophenyl phosphate assay; bone Gla protein (BGP) was measured by radioimmunoassay; type I collagen, matrix metalloproteinase (MMP)-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA were examined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis; MG-63 cells were stained by the Van GieSon method. Type I collagen mRNA expression achieved a maximum level on the 17th day in MG-63 cells; MMP-1 mRNA was not expressed until the 5th day of culture, and gradually increased; TIMP-1 mRNA was nearly constant; ALP activity gradually up-regulated during 0-12 days, and decreased on the 18th day. By Van GieSon staining, MG-63 cells displayed nodule formation at the 12th day, and became more prominent on the 18th day. The results indicate that human osteosarcoma cell line MG-63 has the osteoblast phenotype; during the differentiation of MG-63 cells, there are the following three principle periods: proliferation, extracellular matrix maturation and mineralization.
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PMID:[Differentiation and gene expression of human osteosarcoma cell line MG-63]. 1253 36

Silicon deficiency in animals leads to bone defects. This element may therefore play an important role in bone metabolism. Silicon is absorbed from the diet as orthosilicic acid and concentrations in plasma are 5-20 microM. The in vitro effects of orthosilicic acid (0-50 microM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1). Collagen type 1 mRNA expression and prolyl hydroxylase activity were also determined in the MG-63 cells. Alkaline phosphatase and osteocalcin (osteoblastic differentiation) were assessed both at the protein and the mRNA level in MG-63 cells treated with orthosilicic acid. Collagen type 1 synthesis increased in all treated cells at orthosilicic acid concentrations of 10 and 20 microM, although the effects were more marked in the clonal cell lines (MG-63, HCCl 1.75- and 1.8-fold, respectively, P < 0.001, compared to 1.45-fold in the primary cell lines). Treatment at 50 microM resulted in a smaller increase in collagen type 1 synthesis (MG-63 1.45-fold, P = 0.004). The effect of orthosilicic acid was abolished in the presence of prolyl hydroxylase inhibitors. No change in collagen type 1 mRNA level was seen in treated MG-63 cells. Alkaline phosphatase activity and osteocalcin were significantly increased (1.5, 1.2-fold at concentrations of 10 and 20 microM, respectively, P < 0.05). Gene expression of alkaline phosphatase and osteocalcin also increased significantly following treatment. In conclusion, orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.
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PMID:Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. 1263 84

The aim of the present study was to evaluate and compare the most common parameters that characterize the expression of primary osteoblast cultures from different origin (human, rat, sheep), and of the human osteosarcoma cell line MG-63 before and after stimulation with vitamin 1,25(OH)(2)D(3). Cell viability was quite similar for primary osteoblast cultures (MTT: 1.64-2.11 OD); a significant (P < 0.005) difference was found between sheep osteoblasts and MG-63 (DeltaMTT: 0.52 +/- 0.20 OD). Osteocalcin synthesis ranged from 15.18 to 27.00 pg/ml in primary osteoblast cultures, while it was significantly (P < 0.01) lower in MG-63 (OC: 6.67 +/- 0.52 pg/ml) when compared with primary human osteoblasts. Alkaline phosphatase, C-terminal procollagen type I, and interleukin-6 were significantly (P < 0.005) lower in rat osteoblasts when compared with primary human osteoblasts, and similarly transforming growth factor-beta1 was significantly (P < 0.05) lower in rat and sheep osteoblasts when compared with primary human osteoblasts and MG-63. Nitric oxide synthesis did not show any significant difference either before or after vitamin 1,25(OH)(2)D(3) stimulation. In conclusion, the current findings confirm the presence of interspecies differences between the selected osteoblast lineages before and after stimulation with vitamin 1,25(OH)(2)D(3). Above all, the culture of sheep osteoblasts was seen to behave more similarly to that of primary human cells, mainly in terms of cell viability, osteocalcin, interleukin-6 and transforming growth factor-beta1 production.
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PMID:Comparative interspecies investigation on osteoblast cultures: data on cell viability and synthetic activity. 1264 38

Alkaline phosphatases (ALPs) are a family of cell surface glycoproteins that catalyze the hydrolysis of phosphomonoesters with release of inorganic phosphate. Liver/bone/kidney (L/B/K) ALP participates in bone mineralization, but its other physiological and pathological functions remain obscure. In human osteosarcoma, an inverse relationship has been found between cellular L/B/K ALP expression and aggressiveness. To explore this relationship, we employed cDNA microarray technology to characterize and compare the gene expression profile of two U-2 OS osteosarcoma clones with high L/B/K ALP activity (U-2/ALP28 and U-2/ALP40) and one with contrasting characteristics (U-2/ALP23). We identified 79 differentially expressed genes (58 upregulated in U-2/ALP28 and U-2/ALP40 compared to U-2/ALP23). Using GenMAPP/MAPPFinder, we highlighted nine functional groups strictly related to high L/B/K ALP activity, including microtubule-based movement and cell adhesion groups, two functions well related to tumor invasiveness. Notably, cadherin 13 (CDH13) and caveolin 1 (CAV1) genes were upregulated in our cells. Since these two genes are involved in cell-cell adhesion and cell growth, their co-expression with L/B/K ALP could help explain the lower levels of malignancy found in osteosarcoma cells with high L/B/K ALP activity. Although functional studies are needed to better define the role of CDH13 and CAV1 in the malignant behavior of osteosarcoma cells, the data presented here provide an aid to understanding the biological functions of L/B/K ALP in bone tumors.
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PMID:Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene. 1505 Aug 98

Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine. By means of alkaline phosphatase activity and osteocalcin enzyme-linked immunosorbent assay (ELISA), we have shown that piceatannol exhibits a significant induction of differentiation in immortalized fetal osteoblasts (hFOB), and osteosarcoma cells (MG-63). Alkaline phosphatase and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively, our results indicate that piceatannol stimulate osteoblast differentiation at various stages (from maturation to terminally differentiated osteoblasts). Induction of differentiation by piceatannol was associated with increased bone morphogenetic protein-2 (BMP-2) production. Addition of purified BMP-2 protein did not increase the upregulation of alkaline phosphatase activity and osteocalcin secretion by piceatannol, whereas the BMP-2 antagonist noggin blocked piceatannol and BMP-2-mediated alkaline phosphatase activity, and osteocalcin secretion enhancement, indicating that BMP-2 production is required in piceatannol-mediated osteoblast maturation and differentiation. In conclusion, piceatannol increased BMP-2 synthesis, and this effect may contribute to its action on the induction of osteoblasts maturation and differentiation, followed by an increase of bone mass. Decreases in new bone formation, followed by estrogen deficiency or various pathologic factors, may contribute to the mechanisms involved in postmenopausal osteoporosis.
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PMID:Piceatannol stimulates osteoblast differentiation that may be mediated by increased bone morphogenetic protein-2 production. 1702 90

The aim of this work was to study the in vitro biocompatibility of glass-ceramic scaffolds based on 45S5 Bioglass, using a human osteosarcoma cell line (HOS-TE85). The highly porous scaffolds were produced by the foam replication technique. Two different types of scaffolds with different porosities were analysed. They were coated with a biodegradable polymer, poly(3-hydroxybutyrate) (P(3HB)). The scaffold bioactivity was evaluated by soaking in a simulated body fluid (SBF) for different durations. Compression strength tests were performed before and after immersion in SBF. These experiments showed that the scaffolds are highly bioactive, as after a few days of immersion in SBF a hydroxyapatite-like layer was formed on the scaffold's surface. It was also observed that P(3HB)-coated samples exhibited higher values of compression strength than uncoated samples. Biocompatibility assessment was carried out by qualitative evaluation of cell morphology after different culture periods, using scanning electron microscopy, while cell proliferation was determined by using the AlamarBlue assay. Alkaline phosphatase (ALP) and osteocalcin (OC) assays were used as quantitative in vitro indicators of osteoblast function. Two different types of medium were used for ALP and OC tests: normal supplemented medium and osteogenic medium. HOS cells were seeded and cultured onto the scaffolds for up to 2 weeks. The AlamarBlue assay showed that cells were able to proliferate and grow on the scaffold surface. After 7 days in culture, the P(3HB)-coated samples had a higher number of cells on their surfaces than the uncoated samples. Regarding ALP- and OC-specific activity, no significant differences were found between samples with different pore sizes. All scaffolds containing osteogenic medium seemed to have a slightly higher level of ALP and OC concentration. These experiments confirmed that Bioglass/P(3HB) scaffolds have potential as osteoconductive tissue engineering substrates for maintenance and normal functioning of bone tissue.
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PMID:In vitro biocompatibility of 45S5 Bioglass-derived glass-ceramic scaffolds coated with poly(3-hydroxybutyrate). 1917 Feb 50

The purpose of this study was to prospectively evaluate the use of ultrasonographically guided high-intensity focused ultrasound (HIFU) in the salvage of limbs in patients with osteosarcoma. Seven patients underwent HIFU ablation. Laboratory and radiologic examinations were performed after intervention. Changes in symptoms and survival time were noted at follow-up. No severe complications were observed, and preexisting severe pain disappeared in patients treated with HIFU. Alkaline phosphatase did not show statistically significant changes before and after HIFU treatment, although Alkaline phosphatase did change 1 mo and 2 mo after HIFU. Complete response of the tumor was achieved in three patients with osteosarcoma. Partial response was achieved in another three patients treated with HIFU. Pulmonary metastasis was noted in only one patient 5 mo after HIFU. The median survival time was 68 mo. All patients were alive 3 y after HIFU treatment. Five patients were alive at follow-up visits after 5 y. One patient died from cachexia and infection after 4 y, another patient died of cardiac arrest attack after 4 y. Three patients died of lung dysfunction from pulmonary metastases after 5 y. The five-year survival rate was 71.4%. The authors concluded that HIFU ablation was a safe and feasible method of treatment of osteosarcoma which salvages the limb, but large-scale randomized clinical trials are necessary for confirmation.
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PMID:Osteosarcoma: limb salvaging treatment by ultrasonographically guided high-intensity focused ultrasound. 1944 2

There is little information in veterinary literature regarding the diagnostic accuracy of aspirate cytology for the diagnosis of canine osteosarcoma (OSA). The authors compared the diagnostic accuracy of a novel method of cytologic collection, termed core aspirate cytology (CA), with fine needle aspiration (FNA) and histopathology in 27 dogs with lytic and/or proliferative bone lesions. Alkaline phosphatase (ALP) staining was performed to confirm the diagnosis of OSA cytologically. OSA was accurately diagnosed in 85% and 95% of FNA and CA, respectively. ALP staining was 100% sensitive for the diagnosis of OSA. CA using a bone marrow biopsy needle allowed for penetration of cortical bone and aspirate cytology with a larger bore needle than FNA; however, there was no significant difference in diagnostic accuracy between techniques. Aspirate cytology with ALP staining was a safe, accurate, and minimally invasive diagnostic test for the evaluation of suspected OSA lesions in dogs.
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PMID:A novel method of core aspirate cytology compared to fine-needle aspiration for diagnosing canine osteosarcoma. 2185 7

The objective of this paper is to explore the value of bone alkaline phosphatase (BALP) for diagnosing osteosarcoma, evaluating the effect of the chemotherapy, judging the prognosis and supervising the relapse and metastasis. The immunoassay was used to check the BALP of the blood serum that was from 42 primary osteosarcoma patients. Alkaline phosphatase (ALP) in blood serum was checked with auto biochemistry equipment. The biopsy tissue and the lesion resected in operation were treated with pathology and histological response was counted. The patients were followed up from five months to 49 months with an average of 24.3 months. Eighteen cases relapsed and transferred, among which, 16 of them were dead, and others were survival to the end of the follow-up. BALP was more sensitive than ALP in diagnosing osteosarcoma (P = 0.015). Fifteen cases decreased to normal value in ALP after preoperative chemotherapy, and 34 cases decreased in BALP. Both ALP and BALP in all cases decreased to normal value in post-operative. There was significant difference in positive correlation between the decrease of BALP and the increase of histological response (P = 0.001, r = 0.642). In the follow-up, there was significant difference in BALP between the group of relapse and transfer and the group of free disease survival (P = 0.000). As a check marker in blood serum, BALP, reflecting the process of ossification, has a higher sensitivity than ALP. It has applied value in the diagnosis of osteosarcoma, reflection of the effect of chemotherapy and forecast the prognosis.
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PMID:Measurement of bone alkaline phosphatase and relative study with osteosarcoma. 2455 18


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