Abstract
Osteoclasts begin as mononuclear cells that fuse to form multinuclear cells able to resorb bone. The mechanisms that regulate all the steps of osteoclast differentiation are not entirely known. MYO10, an unconventional myosin, has previously been shown in mature osteoclasts to play a role in attachment and podosome positioning. We determined that MYO10 is also expressed early during osteoclast differentiation. Loss of MYO10 expression in osteoclast precursors inhibits the ability of mononuclear osteoclasts to fuse into multinuclear osteoclasts. Expression of Nfatc1, Dc-stamp, Ctsk, and β3integrin is reduced in the osteoclasts with reduced MYO10 expression. A slight reduction in the osteoclasts ability to migrate, as well as a reduction in SMAD 1/5/8 phosphorylation are also noted with reduced MYO10 expression. Interestingly we also detected a change in the ability of the osteoclast precursors to form tunneling nanotubes (TNTs), which suggests that MYO10 may regulate the presence of TNTs through its interaction with the cytoskeletal proteins.
Highlights
Osteoclasts, which are large multinucleated cells formed from the fusion of multiple mononuclear precursors[1], are the primary resorptive cells of the skeleton
To determine whether MYO10 is expressed during early stages of osteoclast differentiation, protein lysates from different days of RANKL- or RANKL- and BMP2-treated osteoclast cultures were analyzed by Western blot
This study provides compelling evidence that MYO10 expression is necessary for migration of osteoclast precursors during the fusion process
Summary
Osteoclasts, which are large multinucleated cells formed from the fusion of multiple mononuclear precursors[1], are the primary resorptive cells of the skeleton. They facilitate the removal of old bone and aid in maintaining mineral homeostasis[2]. Myosin X (MYO10) is an unconventional myosin It is essential for formation of filopodia, which are slender actin-based extensions in cells[6]. Osteoclast precursors with reduced levels of MYO10 expression remain mononuclear and unable to fuse and differentiate into multinuclear cells. We determined that MYO10 regulates osteoclast migration, tunneling nanotube formation and actin organization necessary for osteoclast fusion
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