INHIBITION OF OSTEOCLAST-LIKE CELL-FORMATION BY BISPHOSPHONATES IN LONG-TERM CULTURES OF HUMAN-BONE MARROW
INHIBITION OF OSTEOCLAST-LIKE CELL-FORMATION BY BISPHOSPHONATES IN LONG-TERM CULTURES OF HUMAN-BONE MARROW
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DOI：
10.1172/jci114100
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发表时间：
1989-06-01
影响因子：
15.9
通讯作者：
GOWEN, M
中科院分区：
文献类型：
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作者：
HUGHES, DE;MACDONALD, BR;GOWEN, M
双膦酸盐通过未知的机制在体内和体外抑制骨吸收。使用人长期骨髓培养物研究了二膦酸盐对从其单核造血前体形成破骨细胞的影响，其中形成了表达破骨细胞表型的大多数已知特征（例如，骨吸收、抗酒石酸酸性磷酸酶、降钙素反应性和与特异性MAb的反应性）。测试的五种双膦酸盐强烈抑制1，25-二羟维生素D3刺激的这些细胞的形成，其相对效力与它们在体内抑制骨吸收相同。两种代表性化合物（3-氨基-1-羟基亚丙基-1，1-二膦酸酯和二氯亚甲基二膦酸酯）不能抑制破骨细胞样细胞前体细胞的增殖。然而，这些化合物降低了表达破骨细胞抗原的单核细胞和多核细胞的比例，从而表明对破骨细胞谱系的细胞具有一定程度的特异性。我们的结论是，双膦酸盐是有效的抑制剂，破骨细胞样细胞的形成在长期的人骨髓培养，这可能与他们的能力，抑制骨吸收在体内。
Bisphosphonates inhibit bone resorption in vivo and in vitro by unknown mechanisms. The effect of bisphosphonates on the formation of osteoclasts from their mononuclear hematopoietic precursors was investigated using human long-term marrow cultures in which multinucleated cells form that express most of the known features of the osteoclast phenotype (e.g., bone resorption, tartrate-resistant acid phosphatase, calcitonin responsiveness, and reactivity with specific MAbs). The five bisphosphonates that were tested strongly inhibited 1,25-dihydroxyvitamin D3-stimulated formation of these cells with the same relative potencies as they inhibit bone resorption in vivo. Two respresentative compounds (3-amino-1-hydroxypropylidene-1,1-bisphosphonate and dichloromethylene bisphosphonate) failed to inhibit the proliferation of precursors of the osteoclast-like cells. However, these compounds decreased the proportion of mononuclear and multinucleated cells expressing an osteoclast antigen, thus suggesting a degree of specificity for cells of the osteoclast lineage. We conclude that bisphosphonates are potent inhibitors of osteoclast-like cell formation in long-term human marrow cultures, and that this may be related to their ability to inhibit bone resorption in vivo.