Simultaneous alterations in ovaries and bone as a result of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most widely recognized endocrine disorders affecting reproductive-age women. The etiopathogenesis and mechanisms of this syndrome remain unclear. Diagnosis requires two of the following: polycystic ovaries, oligo- or anovulation, and hyperandrogenism. Most women with PCOS display conditions such as metabolic abnormalities, diabetes, obesity, cardiovascular disease, and/or bone dysfunction. Considering the ethical limitations of human studies, animal and cell culture models that reflect some features of PCOS are important for investigation of this syndrome. The aim of the present work was to study some of the endocrine relationships between ovaries and bone tissue in a polycystic ovary syndrome animal model. The study was performed using an estradiol valerate PCOS-induced rat model (n = 30) and bone mesenchymal stem cell cultured from bone marrow of those animals. It was hypothesized that changes of the endocrine relationship between ovaries and bones could be observed in from in vivo animal model and in vitro cell culture assays. The ovarian morphological and endocrine changes seem to be correlated with endocrine, biophysical, and biomechanical changes in bone properties. Mesenchymal stem cells obtained from PCOS-induced rats, cultured for up to 21 days and differentiated into osteoblasts, presented lower viability and reduced mineralization of the extracellular matrix. Taken together, these results indicate important endocrine and structural effects of PCOS in ovaries and bones, contributing to part of the understanding of the pathophysiological mechanisms of PCOS

Avaliação da diferenciação osteoblástica de células-tronco mesenquimais de ratos tratados cronicamente com bifosfonatos

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

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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