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  4. Gap junctional communication in human osteoclasts in vitro and in vivo
 
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Gap junctional communication in human osteoclasts in vitro and in vivo

Publikationstyp
Journal Article
Date Issued
2008-12-16
Sprache
English
Author(s)
Schilling, Arndt F.  
Filke, Silke  
Lange, Tobias  
Gebauer, Matthias  
Brink, Silja  
Baranowsky, Anke  
Zustin, Jozef  
Amling, Michael  
Institut
Biomechanik M-3  
TORE-URI
http://hdl.handle.net/11420/4325
Journal
Journal of cellular and molecular medicine  
Volume
12
Issue
6A
Start Page
2497
End Page
2504
Citation
Journal of Cellular and Molecular Medicine 6A (12): 2497-2504 (2008)
Publisher DOI
10.1111/j.1582-4934.2008.00275.x
Scopus ID
2-s2.0-57149130418
Publisher
Wiley-Blackwell
Bone-forming cells are known to be coupled by gap junctions, formed primarily by connexin43 (Cx43). The role of Cx43 in osteoclasts has so far only been studied in rodents, where Cx43 is important for fusion of mononuclear precursors to osteoclasts. Given the potential importance for human diseases with pathologically altered osteoclasts, we asked whether a similar influence of Cx43 can also be observed in osteoclasts of human origin. For this purpose, Cx43 mRNA expression was studied in a time course experiment of human osteoclast differentiation by RT-PCR. Localization of Cx43 in these cells was determined by immunohistochemistry and confocal microscopy. For the assessment of the effect of gap junction inhibition on cell fusion, gap junctions were blocked with heptanol during differentiation of the cells and the cells were then evaluated for multinuclearity. Paraffin sections of healthy bone and bone from patients with Paget's disease and giant cell tumour of the bone were used to study Cx43 expression in vivo. We found mRNA and protein expression of Cx43 in fully differentiated osteoclasts as well as in precursor cells. This expression decreased in the course of differentiation. Consistently, we found a lower expression of Cx43 in osteoclasts than in bone marrow precursor cells in the histology of healthy human bone. Blockade of gap junctional communication by heptanol led to a dose-dependent decrease in multinuclearity, suggesting that gap junctional communication precedes cell fusion of human osteoclasts. Indeed, we found a particularly strong expression of Cx43 in the giant osteoclasts of patients with Paget's disease and giant cell tumour of the bone. These results show that gap junctional communication is important for fusion of human mononuclear precursor cells to osteoclasts and that gap junctional Cx43 might play a role in the regulation of size and multinuclearity of human osteoclasts in vivo. © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Subjects
Cell fusion
Connexin
Cx43
Gap junction
Human osteoclasts
DDC Class
570: Biowissenschaften, Biologie
610: Medizin
620: Ingenieurwissenschaften
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