The role of LFA-1 in osteoclast development induced by co-cultures of mouse bone marrow cells and MC3T3-G2/PA6 cells.
The role of LFA-1 in osteoclast development induced by co-cultures of mouse bone marrow cells and MC3T3-G2/PA6 cells.
复制标题
LFA-1 在小鼠骨髓细胞和 MC3T3-G2/PA6 细胞共培养诱导的破骨细胞发育中的作用。
DOI：
10.1034/j.1600-0765.2002.00610.x
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发表时间：
2002
影响因子：
3.5
通讯作者：
T. Umemoto
中科院分区：
文献类型：
--
作者：
N. Tani;J. Penninger;G. Matsumoto;T. Teranaka;T. Umemoto
白细胞功能相关抗原-1（LFA-1）和细胞间粘附分子-1（ICAM-1）之间的相互作用影响破骨细胞的发育。然而，很少有人知道这些粘附分子是如何参与破骨细胞的发展过程。本研究评价了LFA-1及其配体在破骨细胞发育和骨吸收中的作用。将来自LFA-1缺陷型小鼠的骨髓细胞和MC 3 T3-G2/PA 6（PA 6）细胞的共培养物在1 α，25（OH）2D 3和地塞米松存在下培养7天。来自LFA-1缺陷小鼠的骨髓细胞产生的TRAP阳性细胞的数量小于来自野生型小鼠的骨髓细胞产生的TRAP阳性细胞的数量。此外，从LFA-1缺陷小鼠产生的破骨细胞样细胞的骨吸收活性低于从野生型小鼠产生的破骨细胞样细胞。免疫荧光流式细胞术显示破骨基质PA 6细胞表达细胞粘附分子ICAM-1和VCAM-1。当将抗小鼠VCAM-1、CD 11b或CD 18的单克隆抗体分别加入共培养系统时，从LFA-1缺陷型小鼠产生的TRAP阳性细胞的数量比从野生型小鼠产生的TRAP阳性细胞的数量少20-30%。与添加正常IgG血清相比，抗CD 18抗体尤其抑制来自LFA-1缺陷型和野生型小鼠的TRAP阳性细胞的形成。这些结果表明，LFA-1粘附分子通过在ODF-ODF受体信号传导发生之前影响基质细胞和破骨细胞祖细胞之间的粘附而在破骨细胞发育中发挥作用。在破骨细胞发育的早期阶段，CD 18似乎是细胞与细胞接触的关键粘附分子。
Interactions between leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) influence the development of osteoclasts. However, little is known about how these adhesion molecules are involved in the process of osteoclast development. This study evaluated the role of LFA-1 and its ligands in osteoclast development and bone resorption. Co-cultures of bone marrow cells from LFA-1-deficient mice and MC3T3-G2/PA6 (PA6) cells were cultured in the presence of 1alpha,25(OH)2D3 and dexamethasone for 7 days. The number of TRAP-positive cells that were generated by bone marrow cells from LFA-1-deficient mice was smaller than that generated by bone marrow cells from wild-type mice. In addition, the bone-resorbing activity of osteoclast-like cells that were generated from LFA-1-deficient mice was lower than that generated by osteoclast-like cells from wild-type mice. Immunofluorescence flow cytometry showed that osteoclast stromal PA6 cells expressed the cell adhesion molecules, ICAM-1 and VCAM-1. When monoclonal antibodies to mice VCAM-1, CD11b or CD18 were added separately to the co-culture system, the number of TRAP-positive cells that were generated from LFA-1-deficient mice was 20-30% smaller than that generated from wild-type mice. The formation of TRAP-positive cells from both LFA-1 deficient and wild-type mice was especially inhibited by anti-CD18 antibody, in comparison to the addition of normal IgG serum. These results suggest that LFA-1 adhesion molecules play a role in osteoclast development by affecting adhesion between stromal cells and osteoclast progenitors before the occurrence of ODF-ODF receptor signaling. CD18 appears to be a key adhesion molecule in cell-to-cell contacts during the early stage of osteoclast development.