Exercise is a key lifestyle approach to optimize bone health. Physical activity can influence bone physiology through many ways. We studied at cellular level some biochemical mechanisms involved in the action of sclerostin, a cytokine that negatively affect bone growth and metabolism. This study started from the observation that young rhythmic gymnasts have high levels of circulating sclerostin, in spite of a high degree of bone mineralization, suggesting that exercise is able to neutralize the negative effect of sclerostin on bone growth. In order to study some biochemical aspects of sclerostin, we used SaOS2 osteosarcoma cells, which are osteogenic cells with osteoblastic characteristics. In this experimental model we observed that sclerostin inhibited mineralization and induced apoptosis with caspase activation. The proapoptotic effect of sclerostin was inhibited by inducers of autophagy such as the natural polyamine spermidine, suggesting a possible link between sclerostin and polyamines. Furthermore, also activation of AMP activated protein kinase (AMPK) or of the SIRT1 deacetylase led to protection against sclerostin-induced apoptosis. Interestingly, AMPK and SIRT1 are both associated to exercise. These data suggest a new mechanism whereby fisical exercise can modulate osteogenesis and bone remodelling, that are important pocesses associated to bone health.
Impatto dell'esercizio fisico sulla salute dell'osso: studio sui meccanismi biochimici e cellulari
2017
Abstract
Exercise is a key lifestyle approach to optimize bone health. Physical activity can influence bone physiology through many ways. We studied at cellular level some biochemical mechanisms involved in the action of sclerostin, a cytokine that negatively affect bone growth and metabolism. This study started from the observation that young rhythmic gymnasts have high levels of circulating sclerostin, in spite of a high degree of bone mineralization, suggesting that exercise is able to neutralize the negative effect of sclerostin on bone growth. In order to study some biochemical aspects of sclerostin, we used SaOS2 osteosarcoma cells, which are osteogenic cells with osteoblastic characteristics. In this experimental model we observed that sclerostin inhibited mineralization and induced apoptosis with caspase activation. The proapoptotic effect of sclerostin was inhibited by inducers of autophagy such as the natural polyamine spermidine, suggesting a possible link between sclerostin and polyamines. Furthermore, also activation of AMP activated protein kinase (AMPK) or of the SIRT1 deacetylase led to protection against sclerostin-induced apoptosis. Interestingly, AMPK and SIRT1 are both associated to exercise. These data suggest a new mechanism whereby fisical exercise can modulate osteogenesis and bone remodelling, that are important pocesses associated to bone health.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/346735
URN:NBN:IT:BNCF-346735