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Int J Mol Sci ; 18(12)2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29236045

RESUMO

Osteoarthritis (OA), the most prevalent musculoskeletal pathology, is mainly characterized by the progressive degradation of articular cartilage due to an imbalance between anabolic and catabolic processes. Consequently, OA has been associated with defects in the chondrocitic differentiation of progenitor stem cells (PSCs). In addition, SOX9 is the transcription factor responsible for PSCs chondrogenic commitment. To evaluate the effects of the non-amino bisphosphonate clodronate in OA patients we investigated SOX9 gene expression in circulating progenitor cells (CPCs) and in an in vitro OA model. We evaluated pain intensity, mental and physical performance in OA patients, as well as serum biomarkers related to bone metabolism. In addition, in order to improve therapeutic strategies, we assayed nanoparticle-embedded clodronate (NPs-clo) in an in vitro model of chondrogenic differentiation. Our data showed upregulation of SOX9 gene expression upon treatment, suggesting an increase in chondrocytic commitment. Clodronate also reduced osteoarticular pain and improved mental and physical performance in patients. Furthermore, NPs-clo stimulated SOX9 expression more efficaciously than clodronate alone. Clodronate may therefore be considered a good therapeutic tool against OA; its formulation in nanoparticles may represent a promising challenge to counteract cartilage degeneration.


Assuntos
Ácido Clodrônico/uso terapêutico , Osteoartrite/tratamento farmacológico , Idoso , Biomarcadores/sangue , Diferenciação Celular , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese , Ácido Clodrônico/química , Ácido Clodrônico/farmacologia , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Nanopartículas/química , Osteoartrite/patologia , Dor/patologia , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Índice de Gravidade de Doença , Células-Tronco/citologia , Células-Tronco/metabolismo , Regulação para Cima/efeitos dos fármacos
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