Tunneling Nanotube-Mediated Filamin A Transport Mechanosensitively Programs Osteoclastogenesis in Myeloma Bone Disease - PubMed
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- #filamin A
- #osteoclastogenesis
- #tunneling nanotubes
- Tunneling nanotubes (TNTs) directly connect multiple myeloma (MM) cells and osteoclast precursor cells (pre-OCs).
- Filamin-A (FLNA) is identified as a major protein transported from MM to pre-OCs via TNTs.
- FLNA activates Rho and MAPK signaling pathways, promoting F-actin polymerization and osteoclast differentiation by modulating cellular stiffness, traction force, and deformability.
- FLNA binds vinculin, enhances podosome function and bone resorption capacity of osteoclasts.
- Inhibition of TNTs with Latrunculin B disrupts FLNA transport and alleviates osteolytic bone disease in a myeloma mouse model.