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Gap junctional communication in human osteoclasts in vitro and in vivo.
J Cell Mol Med. 2008 Dec; 12(6A):2497-504.JC

Abstract

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.

Authors+Show Affiliations

Department of Trauma-, Hand- and Reconstructive Surgery, Center for iomechanics and Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18266960

Citation

Schilling, A F., et al. "Gap Junctional Communication in Human Osteoclasts in Vitro and in Vivo." Journal of Cellular and Molecular Medicine, vol. 12, no. 6A, 2008, pp. 2497-504.
Schilling AF, Filke S, Lange T, et al. Gap junctional communication in human osteoclasts in vitro and in vivo. J Cell Mol Med. 2008;12(6A):2497-504.
Schilling, A. F., Filke, S., Lange, T., Gebauer, M., Brink, S., Baranowsky, A., Zustin, J., & Amling, M. (2008). Gap junctional communication in human osteoclasts in vitro and in vivo. Journal of Cellular and Molecular Medicine, 12(6A), 2497-504. https://doi.org/10.1111/j.1582-4934.2008.00275.x
Schilling AF, et al. Gap Junctional Communication in Human Osteoclasts in Vitro and in Vivo. J Cell Mol Med. 2008;12(6A):2497-504. PubMed PMID: 18266960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gap junctional communication in human osteoclasts in vitro and in vivo. AU - Schilling,A F, AU - Filke,S, AU - Lange,T, AU - Gebauer,M, AU - Brink,S, AU - Baranowsky,A, AU - Zustin,J, AU - Amling,M, Y1 - 2008/02/08/ PY - 2008/2/13/pubmed PY - 2009/4/3/medline PY - 2008/2/13/entrez SP - 2497 EP - 504 JF - Journal of cellular and molecular medicine JO - J. Cell. Mol. Med. VL - 12 IS - 6A N2 - 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. SN - 1582-1838 UR - https://www.unboundmedicine.com/medline/citation/18266960/Gap_junctional_communication_in_human_osteoclasts_in_vitro_and_in_vivo_ L2 - https://doi.org/10.1111/j.1582-4934.2008.00275.x DB - PRIME DP - Unbound Medicine ER -