title: The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts.
abstract: Multinucleated osteoclasts are responsible for bone resorption. Hypermultinucleated osteoclasts are often observed in some bone-related diseases such as Paget's disease and cherubism. The cellular mechanics controlling the size of osteoclasts is poorly understood. We introduced EGFP-actin into RAW 264.7 cells to monitor actin dynamics during osteoclast differentiation. Before their terminal differentiation into osteoclasts, syncytia displayed two main types of actin assembly, podosome clusters and clusters of zipper-like structures. The zipper-like structures morphologically resembled the adhesion zippers found at the initial stage of cell-cell adhesion in keratinocytes. In the zipper-like structure, Arp3 and cortactin overlapped with the distribution of dense F-actin, whereas integrin β3, paxillin and vinculin were localized to the periphery of the structure. The structure was negative for WGA-lectin staining and biotin labeling. The zipper-like structure broke down and transformed into a large actin ring, called a podosome belt. Syncytia containing clusters of zipper-like structures had more nuclei than those with podosome clusters. Differentiated osteoclasts with a podosome belt also formed the zipper-like structure at the cell contact site during cell fusion. The breakdown of the cell contact site resulted in the fusion of the podosome belts following plasma membrane fusion. Additionally, osteoclasts in mouse calvariae formed the zipper-like structure in the sealing zone. Therefore, we propose that the zipper-like actin superstructures might be involved in cell-cell interaction to achieve efficient multinucleation of osteoclasts. Understanding of the zipper-like structure might lead to selective therapeutics for bone diseases caused by hypermultinucleated osteoclasts.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan. takito@sc.itc.keio.ac.jp
authors.forename: Jiro
authors.initials: J
authors.lastname: Takito
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoda
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002451:Cell Compartmentation; D002454:Cell Differentiation; D002459:Cell Fusion; D002460:Cell Line; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D000199:Actins