Abstract
Investigations addressing the molecular keys of osteoclast fusion are primarily based on end‐point analyses. No matter if investigations are performed in vivo or in vitro the impact of a given factor is predominantly analyzed by counting the number of multi‐nucleated cells, the number of nuclei per multinucleated cell or TRAcP activity. But end‐point analyses do not show how the fusion came about. This would not be a problem if fusion of osteoclasts was a random process and occurred by the same molecular mechanism from beginning to end. However, we and others have in the recent period published data suggesting that fusion partners may specifically select each other and that heterogeneity between the partners seems to play a role. Therefore, we set out to directly test the hypothesis that fusion factors have a heterogenic involvement at different stages of nuclearity. Therefore, we have analyzed individual fusion events using time‐lapse and antagonists of CD47 and syncytin‐1. All time‐lapse recordings have been studied by two independent observers. A total of 1808 fusion events were analyzed. The present study shows that CD47 and syncytin‐1 have different roles in osteoclast fusion depending on the nuclearity of fusion partners. While CD47 promotes cell fusions involving mono‐nucleated pre‐osteoclasts, syncytin‐1 promotes fusion of two multi‐nucleated osteoclasts, but also reduces the number of fusions between mono‐nucleated pre‐osteoclasts. Furthermore, CD47 seems to mediate fusion mostly through broad contact surfaces between the partners’ cell membrane while syncytin‐1 mediate fusion through phagocytic‐cup like structure. J. Cell. Physiol. 232: 1396–1403, 2017. © 2016 Wiley Periodicals, Inc.
Highlights
Osteoclast Fusion Time-Lapse Reveals Involvement of CD47 and Syncytin-1 at Different Stages of Nuclearity Marie Julie Møller, Anaïs; Delaissé, Jean-Marie; Søe, Kent
The present study shows that CD47 and syncytin-1 have different roles in osteoclast fusion depending on the nuclearity of fusion partners
When analyzing the total number of fusion events, we found that inhibition of CD47 by a mono-clonal antibody reduced the total number of fusion events by approximately 50% compared to control condition (Fig. 1) in the presence of an isotype control antibody
Summary
Osteoclast Fusion Time-Lapse Reveals Involvement of CD47 and Syncytin-1 at Different Stages of Nuclearity Marie Julie Møller, Anaïs; Delaissé, Jean-Marie; Søe, Kent. In order to identify the role of these factors, a series of molecular techniques, and cellular model systems have been employed, which in general are evaluated through end-point measurements by counting the number of multi-nucleated OCs, number of nuclei per OC, resorptive activity, and so forth at the end of the incubation period These analyses are powerful, but are not able to elucidate on the details of individual fusion events leading to this outcome. We have recently published a study (Soe et al, 2015), in which we analyzed a large quantity of time-lapse recordings made over a period of 4 days Using this technique we showed that multi-nucleated OCs preferred to fuse with mononucleated cells, that fusion occurred primarily through a broad contact surface or a phagocytic-cup like structure and that fusion mostly occurred between fusion pairs with divergent motility (Soe et al, 2015)
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