Osteoclast Fusion and Fission

Ineke D C Jansen,Vincent Everts,Veerle Bloemen,Jenny A F Vermeer,Jan Stap

doi:10.1007/s00223-012-9600-y

Ineke D C Jansen, Vincent Everts + Show 3 more

Open Access

https://doi.org/10.1007/s00223-012-9600-y

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Abstract

Osteoclasts are specialized multinucleated cells with the unique capacity to resorb bone. Despite insight into the various steps of the interaction of osteoclast precursors leading to osteoclast formation, surprisingly little is known about what happens with the multinucleated cell itself after it has been formed. Is fusion limited to the short period of its formation, or do osteoclasts have the capacity to change their size and number of nuclei at a later stage? To visualize these processes we analyzed osteoclasts generated in vitro with M-CSF and RANKL from mouse bone marrow and native osteoclasts isolated from rabbit bones by live cell microscopy. We show that osteoclasts fuse not only with mononuclear cells but also with other multinucleated cells. The most intriguing finding was fission of the osteoclasts. Osteoclasts were shown to have the capacity to generate functional multinucleated compartments as well as compartments that contained apoptotic nuclei. These compartments were separated from each other, each giving rise to a novel functional osteoclast or to a compartment that contained apoptotic nuclei. Our findings suggest that osteoclasts have the capacity to regulate their own population in number and function, probably to adapt quickly to changing situations.Electronic supplementary materialThe online version of this article (doi:10.1007/s00223-012-9600-y) contains supplementary material, which is available to authorized users.

Highlights

Osteoclasts are specialized multinucleated cells with the unique capacity to resorb bone
Despite insight into the various steps of the interaction of osteoclast precursors leading to osteoclast formation, surprisingly little is known about what happens with the multinucleated cell itself after it has been formed
Multinucleated osteoclasts proved to have the capacity to split up in different compartments, each part containing a number of nuclei

Summary

Introduction

Osteoclasts are specialized multinucleated cells with the unique capacity to resorb bone. Osteoclasts are multinucleated, polarized cells, with a unique function: resorption of mineralized substrates such as bone, dentin, and mineralized cartilage. They originate from mononuclear hematopoietic cells of the monocyte lineage. The formation of multinucleated bone resorbing osteoclasts is a multistep process comprising (1) recruitment of mononuclear precursors from the bone marrow or peripheral blood, (2) attraction of these cells by bone lining cells. C. Jansen et al.: Osteoclast Fusion and Fission to the bone site where resorption is needed, (3) attachment of the precursors to the bone lining cells [2], (4) a subsequent differentiation of the attached precursors into mononuclear TRAP-positive cells, (5) migration of these osteoclast precursors to the mineralized surface, and (6) fusion and the formation of multinucleated osteoclasts

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