title: Osteoclastogenesis is influenced by modulation of gap junctional communication with antiarrhythmic peptides.
abstract: Osteoclasts are formed by the fusion of mononuclear precursor cells of the monocyte-macrophage lineage. Among several putative mechanisms, gap-junctional intercellular communication (GJC) has been proposed to have a role in osteoclast fusion and bone resorption. We examined the role of GJC in osteoclastogenesis and in vitro bone resorption with mouse bone marrow hematopoietic stem cells and RAW 264.7 cells. Blocking of gap junctions with 18-α-glycyrrhetinic acid (18GA) led to inhibition of osteoclastogenesis and in vitro bone resorption. Similarly, the GJC inhibitor GAP27 inhibited osteoclast formation. GJC modulation with the antiarrhythmic peptides (AAPs) led to increased amounts of multinuclear RAW 264.7 osteoclasts as well as increased number of nuclei per multinuclear cell. In the culture of bone marrow hematopoietic stem cells in the presence of bone marrow stromal cells AAP reduced the number of osteoclasts, and coculture of MC3T3-E1 preosteoblasts with RAW 264.7 macrophages prevented the action of AAPs to promote osteoclastogenesis. The present data indicate that AAPs modulate the fusion of the pure culture of cells of the monocyte-macrophage lineage. However, the fusion is influenced by GJC in cells of the osteoblast lineage.
authors.affiliation: Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Kylmäoja
authors.forename: Hanna
authors.initials: H
authors.lastname: Kokkonen
authors.forename: Kyösti
authors.initials: K
authors.lastname: Kauppinen
authors.forename: Piret
authors.initials: P
authors.lastname: Hussar
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sato
authors.forename: Ketil
authors.initials: K
authors.lastname: Haugan
authors.forename: Bjarne Due
authors.initials: BD
authors.lastname: Larsen
authors.forename: Juha
authors.initials: J
authors.lastname: Tuukkanen
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009842:Oligopeptides / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects
chemical_list: D009842:Oligopeptides; C029579:antiarrhythmic peptide