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.
2017
it
File in questo prodotto:
File Dimensione Formato  
Tesi%20Luna%20%20Rizzo%202017%20finale.pdf

accesso solo da BNCF e BNCR

Tipologia: Altro materiale allegato
Licenza: Tutti i diritti riservati
Dimensione 3 MB
Formato Adobe PDF
3 MB Adobe PDF

I documenti in UNITESI sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/346735
Il codice NBN di questa tesi è URN:NBN:IT:BNCF-346735