RESUMO
Bisphosphonates are chemical analogs of isoprene lipids, which competitively decrease the activity of farnesyl diphosphate synthase in osteoclasts and thus retard prenylation. The non-prenylated small GTPases cannot attach to the membrane of osteoclasts, which decreases their resorptive function and accelerates apoptosis. Strontium ranelate activates the Wnt signal pathway (with participation of calcium-sensitive receptor), increases the replication activity (by changing the function of RANKL/RANK/OPG system) thus suppressing the apoptosis of osteoblasts, and retards the resorptive function by accelerating the apoptosis of osteoclasts.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Difosfonatos/uso terapêutico , Tiofenos/uso terapêutico , Apoptose/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Regulação da Expressão Gênica , Geraniltranstransferase/antagonistas & inibidores , Geraniltranstransferase/genética , Geraniltranstransferase/metabolismo , Humanos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMO
Strontium ranelate (29 µg/ml) and ibandronic acid (50 µM) produced a cytotoxic effect on rat bone marrow myelokaryocytes in vitro. Strontium ranelate increased the number of myelokaryocytes with signs of necrosis, ibandronic acid increased the number of apoptotic and necrotic cells in the 9-day 2D culture of bone marrow cells on the plastic surface of the wells of culture plates. Co-culturing of the bone marrow with 3D matrices with microarc calcium phosphate coating that simulated bone mineral matrix increased intracellular ROS concentration, but abolished the cytotoxic effect of these drugs.
Assuntos
Difosfonatos/farmacologia , Tiofenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Medula Óssea/patologia , Fosfatos de Cálcio/química , Células Cultivadas , Citometria de Fluxo , Ácido Ibandrônico , Necrose/induzido quimicamente , RatosRESUMO
Strontium ranelate (SR) effect on the functional parameters of human blood mononuclear leukocytes culture has been investigated. SR in concentrations of 2.9, 29, and 290 mg/ml produces a dose-dependent decrease in the activity of alkaline phosphatase and the content of calcium and potassium ions in supernatants. In concentrations of 2.9 and 29 mg/ml, SR decreases, while in a concentration of 290 mg/ml it increases the intercellular phosphate ion content. Fibroblast- and osteoblast-like cells, which are capable of regulating mineral compound of intercellular liquid, are SR cellular targets in human blood mononuclear leukocytes culture.
