Vanadium derivatives act as growth factor-mimetic compounds upon differentiation and proliferation of osteoblast-like UMR106 cells

The effect of different vanadium compounds on proliferation and differentiation was examined in osteoblast-like UMR106 cells. Vanadate increased the cell growth in a biphasic manner, the higher doses inhibiting cell progression. Vanadyl stimulated cell proliferation in a dose-responsive manner. Similar to vanadate, pervanadate increased osteoblast-like cell proliferation in a biphasic manner but no inhibition of growth was observed. Vanadyl and pervanadate were stronger stimulators of cell growth than vanadate. Only vanadate was able to regulate the cell differentiation as measured by cell alkaline phosphatase activity. These results suggest that vanadium derivatives behave like growth factors on osteoblast-like cells and are potential pharmacological tools in the control of cell growth.Facultad de Ciencias Exacta

A vanadium/aspirin complex controlled release using a poly(ß-propiolactone) film : Effects on osteosarcoma cells

A delivery system for vanadium was developed using poly(ß-propiolactone)(PßPL) films. The release kinetics of a complex of vanadium (IV) with aspirin (VOAspi) was evaluated with lms prepared from polymers of different molecular weights, as well as with variable drug load. A sustained release of vanadium over 7 days was achieved. The drug release kinetics depends on contributions from two factors: (a) diffusion of the drug; and (b) erosion of the PßPL lm. The experimental data at an early stage of release were tted with a diffusion model, which allowed determination of the diffusion coef cient of the drug. VOAspi does not show strong interaction with the polymer, as demonstrated by the low apparent partition coef cient (approximately 10-2). UMR106 osteosarcoma cells were used as a model to evaluate the anticarcinogenic effects of the VOAspi released from the PßPL lm. VOAspi–PßPL lm inhibited cell proliferation in a dose-response manner and induced formation of approximately half of the thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, compared to that with free VOAspi in solution. The unloaded PßPL lm did not generate cytotoxicity, as evaluated by cell growth and TBARS. Thus, the polymer-embedded VOAspi retained the antiproliferative effects showing lower cytotoxicity than the free drug. Results with VOAspi–PßPL lms suggest that this delivery system may have promising biomedical and therapeutic applications.Facultad de Ciencias Exacta

A vanadium/aspirin complex controlled release using a poly(ß-propiolactone) film : Effects on osteosarcoma cells

A delivery system for vanadium was developed using poly(ß-propiolactone)(PßPL) films. The release kinetics of a complex of vanadium (IV) with aspirin (VOAspi) was evaluated with lms prepared from polymers of different molecular weights, as well as with variable drug load. A sustained release of vanadium over 7 days was achieved. The drug release kinetics depends on contributions from two factors: (a) diffusion of the drug; and (b) erosion of the PßPL lm. The experimental data at an early stage of release were tted with a diffusion model, which allowed determination of the diffusion coef cient of the drug. VOAspi does not show strong interaction with the polymer, as demonstrated by the low apparent partition coef cient (approximately 10-2). UMR106 osteosarcoma cells were used as a model to evaluate the anticarcinogenic effects of the VOAspi released from the PßPL lm. VOAspi–PßPL lm inhibited cell proliferation in a dose-response manner and induced formation of approximately half of the thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, compared to that with free VOAspi in solution. The unloaded PßPL lm did not generate cytotoxicity, as evaluated by cell growth and TBARS. Thus, the polymer-embedded VOAspi retained the antiproliferative effects showing lower cytotoxicity than the free drug. Results with VOAspi–PßPL lms suggest that this delivery system may have promising biomedical and therapeutic applications.Facultad de Ciencias Exacta

Advanced glycation endproduct-specific receptors in rat and mouse osteoblast-like cells: regulation with stages of differentiation

Advanced glycation endproducts have been implicated in the development of diabetic complications. In addition, these products could also mediate certain bone alterations such as diabetic osteopenia. Several receptors specific for advanced glycation endproduct-modified proteins have been characterized in different cell types, contributing to the recognition and degradation of senescent proteins. In the present report, we investigated the possible presence of advanced glycation endproduct-binding proteins on osteoblast-like cells. Both UMR106 and MC3T3E1 cell lines express specific advanced glycation endproduct-binding sites, with an affinity constant between 0.4 and 1.7. 10(6) M(-1), depending on the stage of osteoblastic differentiation; and with a receptor capacity of 1.5-2.0. 10(7) sites/cell. Osteoblast-like cells were also found to participate both in the uptake and degradation of advanced glycation endproduct-modified bovine serum albumin at 37 degrees C. Radiolabelled ligand blotting studies confirmed the presence of several membrane binding proteins, with apparent molecular masses of 50, 45-40, 30, 25 and 18 kDa; the major bands corresponded to 30 and 25 kDa proteins. This study provides evidence of the presence of advanced glycation endproduct-specific binding sites, and for their regulation with the stage of differentiation, in two osteoblast-like cells in culture.Facultad de Ciencias Exacta

A vanadium / aspirin complex controlled release using a poly(ß-propiolactone) lm.

A delivery system for vanadiumwas developed using poly(¯-propiolactone)(P¯PL) lms. The release kinetics of a complex of vanadium (IV) with aspirin (VOAspi) was evaluated with lms prepared from polymers of differentmolecularweights, as well as with variable drug load. A sustained release of vanadium over 7 days was achieved. The drug release kinetics depends on contributions from two factors: (a) diffusion of the drug; and (b) erosion of the P¯PL lm. The experimental data at an early stage of release were tted with a diffusion model, which allowed determination of the diffusion coef cient of the drug. VOAspi does not show strong interaction with the polymer, as demonstrated by the low apparent partition coef cient (approximately 10¡2). UMR106 osteosarcoma cells were used as a model to evaluate the anticarcinogenic effects of the VOAspi released from the P¯PL lm. VOAspi–P¯PL lm inhibited cell proliferation in a dose-response manner and induced formation of approximately half of the thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, compared to that with free VOAspi in solution. The unloaded P¯PL lm did not generate cytotoxicity, as evaluated by cell growth and TBARS. Thus, the polymer-embedded VOAspi retained the antiproliferative effects showing lower cytotoxicity than the free drug. Results with VOAspi–P¯PL lms suggest that this delivery system may have promising biomedical and therapeutic applications

Advanced glycation endproduct-specific receptors in rat and mouse osteoblast-like cells: regulation with stages of differentiation

Advanced glycation endproducts have been implicated in the development of diabetic complications. In addition, these products could also mediate certain bone alterations such as diabetic osteopenia. Several receptors specific for advanced glycation endproduct-modified proteins have been characterized in different cell types, contributing to the recognition and degradation of senescent proteins. In the present report, we investigated the possible presence of advanced glycation endproduct-binding proteins on osteoblast-like cells. Both UMR106 and MC3T3E1 cell lines express specific advanced glycation endproduct-binding sites, with an affinity constant between 0.4 and 1.7. 10(6) M(-1), depending on the stage of osteoblastic differentiation; and with a receptor capacity of 1.5-2.0. 10(7) sites/cell. Osteoblast-like cells were also found to participate both in the uptake and degradation of advanced glycation endproduct-modified bovine serum albumin at 37 degrees C. Radiolabelled ligand blotting studies confirmed the presence of several membrane binding proteins, with apparent molecular masses of 50, 45-40, 30, 25 and 18 kDa; the major bands corresponded to 30 and 25 kDa proteins. This study provides evidence of the presence of advanced glycation endproduct-specific binding sites, and for their regulation with the stage of differentiation, in two osteoblast-like cells in culture.Facultad de Ciencias Exacta

Vanadium Compounds : Their Action on Alkaline Phosphatase Activity

The direct effect of different vanadium compounds upon alkaline phosphatase (ALP) activity was investigated~ Vanadate and vanadyl inhibited both the soluble and particulate ALP activity from UMR.106 cells and front bovine intestinal ALP. We have also shown the inhibition of ALP activity in the soluble fraction of osteoblasts by peroxo and hydroperoxo vanadium compounds. ALP activity in the particulate fraction was not inhibited by these species; nor was the bovine intestinal ALP. Using inhibitors of Tyr-phosphatase (PTPases), the soluble ALP was partially characterized as a PTPase. The major activity in the particulate fraction represents the bone-specific ALPactivity. This study demonstrates that different forms of vanadium are direct inhibitors of ALP activity. This effect is dependent on the enzymatic activity investigated and on the origin of the ALP.Facultad de Ciencias Médica

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation

Nitric oxide NO. has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells UMR106 and MC3T3E1. incubated with different concentrations 2.5–100 mM. of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 mM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible eNOS and iNOS. isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca2q-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells. q2000 Elsevier Science B.V. All rights reserved

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation

Nitric oxide NO. has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells UMR106 and MC3T3E1. incubated with different concentrations 2.5–100 mM. of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 mM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible eNOS and iNOS. isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca2q-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells.Facultad de Ciencias Exacta

Vanadium derivatives act as growth factor--mimetic compounds upon differentiation and proliferation of osteoblast-like UMR106 cells

The effect of different vanadium compounds on proliferation and differentiation was examined in osteoblast-like UMR106 cells. Vanadate increased the cell growth in a biphasic manner, the higher doses inhibiting cell progression. Vanadyl stimulated cell proliferation in a dose-responsive manner. Similar to vanadate, pervanadate increased osteoblast-like cell proliferation in a biphasic manner but no inhibition of growth was observed. Vanadyl and pervanadate were stronger stimulators of cell growth than vanadate. Only vanadate was able to regulate the cell differentiation as measured by cell alkaline phosphatase activity. These results suggest that vanadium derivatives behave like growth factors on osteoblast-like cells and are potential pharmacological tools in the control of cell growth