Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
Calcif Tissue Int. 2013 Mar;92(3):270-81. doi: 10.1007/s00223-012-9680-8. Epub 2012 Dec 16.
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.
破骨细胞是由单核细胞-巨噬细胞谱系的单核细胞前体细胞融合而成的。在几种可能的机制中，缝隙连接细胞间通讯（GJC）被认为在破骨细胞融合和骨吸收中起作用。我们使用小鼠骨髓造血干细胞和 RAW 264.7 细胞检查了 GJC 在破骨细胞发生和体外骨吸收中的作用。用 18-α-甘草次酸（18GA）阻断缝隙连接导致破骨细胞发生和体外骨吸收的抑制。同样，GJC 抑制剂 GAP27 抑制破骨细胞形成。用抗心律失常肽（AAPs）调节 GJC 导致多核 RAW 264.7 破骨细胞数量增加，以及多核细胞中的细胞核数量增加。在骨髓基质细胞存在的情况下培养骨髓造血干细胞时，AAP 减少了破骨细胞的数量，并且 MC3T3-E1 成骨细胞与 RAW 264.7 巨噬细胞共培养可防止 AAP 促进破骨细胞发生的作用。本数据表明，AAP 调节单核细胞-巨噬细胞谱系的纯培养细胞的融合。然而，融合受成骨细胞谱系细胞中的 GJC 影响。
