title: New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts.
abstract: The cytoskeleton mediates various cellular processes such as differentiation and fusion, including in the filopodia and podosomes. However, apart from cell migration and formation of the sealing zone, little is known regarding the changes and related regulatory mechanisms of the cytoskeleton and additional roles of the filopodia and podosomes during the differentiation and fusion of osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the differentiation process were evaluated using tartrate-resistant acid phosphatase staining and immunofluorescence staining. Moreover, the expression levels of Rho GTPases and enzymes related to osteoclast differentiation and bone resorption were detected by quantitative reverse transcription-polymerase chain reaction. We detected 3 types of filopodia in osteoclast precursors and only 1 type of filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of filopodia. Interestingly, cell fusion was highly specific, and the fusion initially occurred to the filopodia. Confocal images revealed that F-actin and microtubules significantly differed among fused cells. These results suggest that filopodia and podosomes not only play important roles in cell migration and the formation of sealing zones but also in the pre-fusion selectivity of 2 cells and the movement direction of the cell nucleus and cytoplasm during the fusion process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types of filopodia during various stages of differentiation, while Rac1, Rac2, and filament A may be associated with cell selectivity during the fusion process.
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: R L
authors: RL
authors: Song
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: X Z
authors: XZ
authors: Liu
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: J Q
authors: JQ
authors: Zhu
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: J M
authors: JM
authors: Zhang
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: Q
authors: Q
authors: Gao
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: H Y
authors: HY
authors: Zhao
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: A Z
authors: AZ
authors: Sheng
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: Y
authors: Y
authors: Yuan
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: J H
authors: JH
authors: Gu
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: H
authors: H
authors: Zou
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
authors: Q C
authors: QC
authors: Wang
authors: College of Veterinary Medicine, Yangzhou University, Yangzhou, China liuzongping@yzu.edu.cn.
authors: Z P
authors: ZP
authors: Liu
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002459:Cell Fusion; D002460:Cell Line; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D064448:Filamins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism* / Q000648:ultrastructure; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D000071681:Tartrate-Resistant Acid Phosphatase; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C499636:DC-STAMP protein, mouse; D064448:Filamins; C529499:FlnA protein, mouse; D007527:Isoenzymes; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020741:rho GTP-Binding Proteins