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Laboratorio de Biología Celular, INTA, Universidad de Chile, El Líbano 5524, Macul. Casilla 138-11, Santiago, Chile
¹ Laboratorio de Envejecimiento y Enfermedades Crónicas Relacionadas con la Nutrición, INTA, Universidad de Chile, Santiago, Chile
² Servicio de Traumatología, Hospital Sótero del Río, Santiago, Chile

(Requests for offprints should be addressed to J P Rodríguez; Email: jprodrig{at}inta.cl)

Human mesenchymal stem cells (hMSCs) are multipotent cells present in bone marrow, which differentiate into osteoblasts and adipocytes, among other lineages. Oestrogens play a critical role in bone metabolism; its action may affect the adipocyte to osteoblast ratio in the bone marrow. In hMSCs, oestrogens are synthesized from C19 steroids by the enzyme aromatase cytochrome P450. In this study, we assessed whether aromatase enzymatic activity varied through early osteogenic (OS) and adipogenic (AD) differentiation. Also, we studied the effect of leptin and 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D₃) on aromatase cell activity. Finally, we analysed whether conditions that modify oestrogen generation by cells affected hMSCs differentiation. For these purposes, hMSCs derived from post-menopausal women (65–86 years old) were cultured under basal, OS or AD conditions, in the presence or the absence of leptin and 1,25(OH)₂D₃. Aromatase activity was measured by the tritiated water release assay and by direct measurement of steroids synthesized from ³H-labelled androstenedione or testosterone. Our results showed that different OS and AD patterns of aromatase activity developed during the first period of differentiation (up to 7 days). A massive and sharp surge of aromatase activity at 24 h characterized early OS differentiation, while increased but constant aromatase activity was increased through adipogenesis. Both leptin and vitamin D increased aromatase activity during osteogenesis, but not during adipogenesis; finally, we showed that favourable aromatase substrates concentration restrained MSCs adipogenesis but improved osteogenesis. Thus, it could be inferred that a high and early increase of local oestrogen concentration in hMSCs affects their commitment either restraining AD or facilitating OS differentiation, or both.