Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures
Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures
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DOI：
10.1016/8756-3282(95)00426-2
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发表时间：
1996-01-01
期刊：
影响因子：
4.1
通讯作者：
Nagata, N
中科院分区：
文献类型：
--
作者：
Nishikawa, M;Akatsu, T;Nagata, N
我们利用含有或不含有成骨细胞的小鼠骨髓培养，研究了双膦酸盐对破骨细胞募集的作用方式。培养形成的抗酒石酸酸性磷酸酶阳性多核细胞[TRAP(+)MNC]经鉴定为破骨细胞。在骨髓培养中，在10(-8)m ol/L 1，25(OH)(2)D-3存在下，加入10(-6)m o l/L二氢(环庚氨基)-亚甲基二膦酸单水合物(YM175)不影响TRAP(+)MNC的形成。然而，在骨髓细胞与成骨细胞共培养中，它被抑制。在整个培养过程中，抑制作用明显，YM175呈剂量依赖性抑制TRAP(+)单核细胞的形成，其他双膦酸盐-帕米磷酸钠和阿伦磷酸酯-也抑制共培养中TRAP(+)单核细胞的形成。在脾细胞和成骨细胞的共培养中也有类似的观察结果。10(-6)mol/L处理的成骨细胞条件培养液可抑制骨髓培养中TRAP(+)单核细胞的形成。在甲基纤维素培养中，YM175的存在既不影响单核-巨噬细胞系的集落形成，也不影响随后回收的细胞与成骨细胞共培养中TRAP(+)MNC的形成。这些结果表明，YM175和其他可能的双膦酸盐也是通过作用于成骨细胞而优先抑制破骨细胞形成的后期阶段。我们的研究结果表明，成骨细胞在双膦酸盐存在下的部分抑制作用是通过可溶性因子介导的(S)。
We examined the mode of action of bisphosphonates on osteoclastic cell recruitment using mouse marrow cultures with or without osteoblastic cells. Tartrate-resistant acid phosphatase-positive multinucleated cells [TRAP(+) MNC] formed in cultures were determined to be osteoclastic cells. In marrow cultures, TRAP(+) MNC formation in the presence of 10(-8) mol/L 1,25(OH)(2)D-3 was not affected by the addition of 10(-6) mol/L dihydrogen (cycloheptylamino)-methylenebisphosphonate monohydrate (YM175). However, it was inhibited in cocultures of marrow cells with osteoblastic cells. The inhibitory effect was evident throughout the entire culture period, YM175 dose dependently inhibited TRAP(+) MNC formation, and other bisphosphonates-pamidronate and alendronate-also inhibited TRAP(+) MNC formation in the coculture. Similar observations were also made in the coculture of spleen cells with osteoblastic cells. The conditioned media of osteoblastic cells treated with 10(-6) mol/L, YM175 inhibited TRAP(+) MNC formation in marrow cultures. The presence of YM175 in methylcellulose cultures affected neither the colony formation of monocyte-macrophage lineage, nor TRAP(+) MNC formation in the succeeding cocultures of recovered cells with osteoblastic cells. These results indicate that YM175 and probably other bisphosphonates as well preferentially inhibit the later stage of osteoclastogenesis through its action on osteoblastic cells. Our findings suggest that part of the inhibitory action by osteoblastic cells in the presence of bisphosphonates is mediated through soluble factor(s).