Destrin deletion enhances the bone loss in hindlimb suspended mice

Abstract

Destrin, also known as actin depolymerizing factor (ADF), is a member of the ADF/Cofilin/destrin superfamily that has the ability to rapidly depolymerize F-actin in a stoichiometric manner. Remodeling of the actin cytoskeleton through actin dynamics (assembly and disassembly of filamentous actin) is known to be essential for numerous basic biological processes including bone formation. The aim of current study was to elucidate whether destrin was involved in the progression of bone loss induced by modeled microgravity. We used the hindlimb suspension (HLS) mice model to simulate microgravity in vivo. Exposure to HLS in mice enhanced femur destrin expression. Destrin deletion in Dstn (-/-) mutant mice enhanced HLS-induced reduction of BMD, ultimate load, stiffness, trabecular thickness, trabecular number, and bone volume fraction in femur, but did not affect them under control static condition. The Rotary wall vessel bioreactor was used to model microgravity in vitro. Exposure to modeled microgravity in cultured 2T3 murine osteoblast precursor cells upregulated destrin expression. RNAi-mediated destrin knockdown enhanced the microgravity-induced reduction of osteoblastic proliferation and differentiation significantly. In conclusion, for the first time we demonstrated that destrin deletion enhances the bone loss in hindlimb suspended mice. Destrin may be a potential target for the prevention or management of microgravity-induced bone loss.