New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

Abstract

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 New roles of filopodia and podosomes of osteoclasts 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 prefusion 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.

Inhibition of osteoclast bone resorption activity through osteoprotegerin-induced damage of the sealing zone

“…A number of studies have also confirmed that RhoGTPases control F-actin polymerization and adhesion, and play an important role in the formation of the sealing zone in osteoclasts (29)(30)(31)(32)(33). As shown by our previous study (34) and a study by other researchers (18), RhoH, RhoJ/TCL and RhoE/Rnd3 are not expressed during osteoclast differentiation and maturation. In addition, the expression of RhoQ/TC10, RhoV/Chp1 and RhoBTB2 is markedly inhibited during the formation of osteoclasts.…”

Tumor Cell Invadopodia: Invasive Protrusions that Orchestrate Metastasis

“…Invadosomes have been described in a variety of normal cell types, including osteoclasts [80], macrophages [79], endothelial cells [81] and neurons [82] in normal physiological contexts, and in tumor cells [79]. The term “invadosome” also includes macrophage podosomes and tumor cell invadopodia but these have well-documented differences in structure, molecular pathways, and functions.…”

Conditional Disruption of miR17∼92 in Osteoclasts Led to Activation of Osteoclasts and Loss of Trabecular Bone in Part Through Suppression of the miR17‐Mediated Downregulation of Protein‐Tyrosine Phosphatase‐oc in Mice

“…There is increasing evidence that activation of Rac1 and/or Rac2 in osteoclasts may play an essential role in osteoclast fusion . Rac1/Rac2 activation (through PTP‐oc‐dependent β 3 ‐integrin‐mediated activation of Vav3) is a key downstream component of the PTP‐oc/EphA4 pathway in osteoclasts .…”