Avaliação da diferenciação osteoblástica de células-tronco mesenquimais de ratos tratados cronicamente com bifosfonatos
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Abstract
Apesar dos bifosfonatos (BPs), fármacos antirreabsortivos, atuarem principalmente nos osteoclastos, a ação desses medicamentos em osteoblastos tem sido demonstrada em experimentos in vitro. Porém, na maioria desses experimentos, há exposição das culturas de osteoblastos aos BPs. Na presente investigação, foram avaliados osteoblastos diferenciados a partir de células-tronco mesenquimais (CTMs) de ratos tratados in vivo com alendronato de sódio (ALE: 1mg/ml/kg/semana), ácido zoledrônico (ZOL: 0,3mg/ml/kg/semana) ou solução salina (VEH: 0,009mg/ml/kg/semana) durante 13 semanas. As CTMs da medula óssea dos fêmures direitos dos animais foram cultivadas em meio osteogênico, na densidade de 5.000 células/200μl/poço. Após 21 dias de cultura, osteoblastos foram avaliados quanto à viabilidade celular e à formação de matriz mineralizada. Foram observadas viabilidades celulares semelhantes nos grupos BPs (ALE e ZOL) e superiores ao controle (VEH). Quanto à formação da matriz mineralizada, houve maior mineralização no grupo ZOL em relação ao grupo ALE, sendo ambas inferiores ao observado no grupo VEH. Os resultados obtidos sugerem que a exposição in vivo das CTMs ao ALE e ao ZOL influenciou a atividade dos osteoblastos in vitro. Ambos os medicamentos utilizados são BPs nitrogenados; contudo, na dose empregada, o ALE afetou mais significativamente a formação de matriz mineralizada.
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