Research ArticleMechanotransduction

Microtubules tune mechanotransduction through NOX2 and TRPV4 to decrease sclerostin abundance in osteocytes

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Science Signaling  21 Nov 2017:
Vol. 10, Issue 506, eaan5748
DOI: 10.1126/scisignal.aan5748

Microtubule stability determines mechanosensitivity

In response to increased mechanical load, osteocytes promote bone formation by reducing the abundance of sclerostin, an inhibitor of the cells that build bone. Lyons et al. found that mechanical stress activated reactive oxygen species production and Ca2+ influx to decrease sclerostin abundance in cultured osteocytes. The sensitivity of this pathway to mechanical stress correlated with the extent of a particular posttranslational modification called detyrosination, which stabilizes the microtubule network. Thus, pharmacological manipulations that alter microtubule detyrosination in osteocytes could be an effective strategy to counteract conditions characterized by low bone density.

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