Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity—Potential Implications for Drug Sensitivity

Søe, Kent

doi:10.3390/ijms21207717

Cited by 39 publications

(29 citation statements)

References 124 publications

(169 reference statements)

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“…between two macrophages or two OC precursors) and ‘heterotypic’ when fusion occurs between different cell types. To account for the complexity of the fusion processes, we will also discuss the possibility of fusion between cells having a common origin but being at different stages of differentiation, in particular in the case of fusion of OC precursors [ 13 , 14 ].…”

Section: Different Types Of Multinucleated Giant Cells From the Monocytic Lineagementioning

confidence: 99%

Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune

Dufrançais

Mascarau

Poincloux

et al. 2021

Cell. Mol. Life Sci.

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Different types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in bone homeostasis. MGCs are formed by cell-to-cell fusion, and most types have been observed in pathological conditions, especially in infectious and non-infectious chronic inflammatory contexts. The precise role of the different MGCs and the mechanisms that govern their formation remain poorly understood, likely due to their heterogeneity. First, we will introduce the main populations of MGCs derived from the monocyte/macrophage lineage. We will then discuss the known molecular actors mediating the early stages of fusion, focusing on cell-surface receptors involved in the cell-to-cell adhesion steps that ultimately lead to multinucleation. Given that cell-to-cell fusion is a complex and well-coordinated process, we will also describe what is currently known about the evolution of F-actin-based structures involved in macrophage fusion, i.e., podosomes, zipper-like structures, and tunneling nanotubes (TNT). Finally, the localization and potential role of the key fusion mediators related to the formation of these F-actin structures will be discussed. This review intends to present the current status of knowledge of the molecular and cellular mechanisms supporting multinucleation of myeloid cells, highlighting the gaps still existing, and contributing to the proposition of potential disease-specific MGC markers and/or therapeutic targets.

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Section: Different Types Of Multinucleated Giant Cells From the Monocytic Lineagementioning

confidence: 99%

Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune

Dufrançais

Mascarau

Poincloux

et al. 2021

Cell. Mol. Life Sci.

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“…This might be attributed to the fact that both macrophages and stem cells possess fusogenic capacities [20][21][22][23][24][25][26][27][30][31][32][33][34][35][36][38][39][40]52]. For instance, it is well known that macrophages give rise to multinucleated osteoclasts through hybridization [7,53,54] and that stem cells could restore degenerated tissues by cell-cell fusion [55][56][57][58].…”

Section: In Vitro and In Vivo Data Supporting Cell-cell Fusion In Cancermentioning

confidence: 99%

Cell–Cell Fusion and the Roads to Novel Properties of Tumor Hybrid Cells

Sieler

Weiler

Dittmar

2021

Cells

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The phenomenon of cancer cell–cell fusion is commonly associated with the origin of more malignant tumor cells exhibiting novel properties, such as increased drug resistance or an enhanced metastatic capacity. However, the whole process of cell–cell fusion is still not well understood and seems to be rather inefficient since only a certain number of (cancer) cells are capable of fusing and only a rather small population of fused tumor hybrids will survive at all. The low survivability of tumor hybrids is attributed to post-fusion processes, which are characterized by the random segregation of mixed parental chromosomes, the induction of aneuploidy and further random chromosomal aberrations and genetic/epigenetic alterations in daughter cells. As post-fusion processes also run in a unique manner in surviving tumor hybrids, the occurrence of novel properties could thus also be a random event, whereby it might be speculated that the tumor microenvironment and its spatial habitats could direct evolving tumor hybrids towards a specific phenotype.

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“…A prerequisite for bone resorption involves a series of complex events that osteoclast precursors must undergo, including attraction/migration, recognition, adhesion, membrane fusion, and finally, formation of giant multinucleated cells (13). These events are mainly attributed to DC-STAMP, osteopontin (OPN), Atp6v0d2 and CD47 among others, and defects in these genes inevitably lead to the generation of inactive osteoclasts (26). DC-STAMP, a membrane-bound receptor, with no definite ligand, is the main regulator of pre-osteoclast fusion (26).…”

Section: Migration Adhesion and Fusionmentioning

confidence: 99%