Osteoclastogenesis is Influenced by Modulation of Gap Junctional Communication with Antiarrhythmic Peptides

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• 作者：Elina Kylm?oja (1)
  Hanna Kokkonen (1)
  Ky?sti Kauppinen (1)
  Piret Hussar (2)
  Tetsuji Sato (3)
  Ketil Haugan (4)
  Bjarne Due Larsen (5)
  Juha Tuukkanen (1)
  
• 关键词：Connexin ; 43 ; Bone resorption ; Osteoclast ; Antiarrhythmic peptide ; GAP27 ; Cell fusion
• 刊名：Calcified Tissue International
• 出版年：2013
• 出版时间：March 2013
• 年：2013
• 卷：92
• 期：3
• 页码：270-281
• 全文大小：1181KB
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• 作者单位：Elina Kylm?oja (1)
  Hanna Kokkonen (1)
  Ky?sti Kauppinen (1)
  Piret Hussar (2)
  Tetsuji Sato (3)
  Ketil Haugan (4)
  Bjarne Due Larsen (5)
  Juha Tuukkanen (1)
  
  1. Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland
  2. Institute of Anatomy, Chair of Histology and Embryology, University of Tartu, Tartu, Estonia
  3. Department of Anatomy (Division II), Tsurumi University School of Dental Medicine, Tsurumi 2-1-3, Tsurumi-Ku, Yokohama, 230-8501, Japan
  4. Department of Cardiology, Roskilde University Hospital, Roskilde, Denmark
  5. Zealand Pharma A/S, Glostrup, Copenhagen, Denmark
  
• ISSN：1432-0827

文摘

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.