1,25-Dihydroxyvitamin D3 causes formation of multinucleated cells with several osteoclast characteristics in cultures of primate marrow.
1,25-Dihydroxyvitamin D3 causes formation of multinucleated cells with several osteoclast characteristics in cultures of primate marrow.
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1,25-二羟基维生素 D3 在灵长类骨髓培养物中引起具有多种破骨细胞特征的多核细胞的形成。
DOI：
10.1073/pnas.82.23.8213
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发表时间：
1985
影响因子：
11.1
通讯作者：
G. Mundy
中科院分区：
文献类型：
--
作者：
G. Roodman;K. Ibbotson;B. R. Macdonald;T. Kuehl;G. Mundy
1，25-二羟基维生素D3在体外可诱导HL-60、U937等单核巨噬细胞分化为巨噬细胞样细胞，并使肺泡巨噬细胞形成多核细胞。由于破骨细胞被认为来自巨噬细胞谱系的早期骨髓细胞，我们在含有1，25-二羟基维生素D3的培养液中培养了正常的灵长类骨髓单个核细胞。我们发现在培养2-3周后形成大的多核细胞(每个细胞3-30个核)。加入1，25-二羟基维生素D3可显著促进多核细胞的形成。其他维生素D类似物甲状旁腺激素、前列腺素E2和降钙素未能刺激多核细胞的形成。然而，降钙素抑制1，25-二羟基维生素D3对多核细胞形成的刺激作用。在这些培养中形成的多核细胞含有抗酒石酸酸性磷酸酶活性，这是破骨细胞的标志酶。这种活性被1，25-二羟基维生素D3和甲状旁腺激素增强，降钙素则抑制这些化合物刺激的酸性磷酸酶活性的增加。在超微结构上，多核细胞有几个类似于破骨细胞的特征。这些数据表明，我们培养的多核细胞具有破骨细胞的一些特征，1，25-二羟基维生素D3在体内和体外的强骨吸收活性可能部分是通过刺激骨髓单个核细胞形成破骨细胞而介导的。
1,25-Dihydroxyvitamin D3 induces cells derived from mononuclear phagocytes such as HL-60 and U937 to differentiate to macrophage-like cells and causes alveolar macrophages to form multinucleated cells in vitro. Since the osteoclast is thought to be derived from early marrow cells of the macrophage lineage, we cultured normal primate marrow mononuclear cells in medium containing 1,25-dihydroxy-vitamin D3. We found that large multinucleated cells (3-30 nuclei per cell) formed after 2-3 weeks of culture. Addition of 1,25-dihydroxyvitamin D3 to these cultures markedly stimulated multinucleated cell formation. Other vitamin D analogues, parathyroid hormone, prostaglandin E2, and calcitonin failed to stimulate multinucleated cell formation. However, calcitonin inhibited the stimulation of multinucleated cell formation by 1,25-dihydroxyvitamin D3. The multinucleated cells that formed in these cultures contained a tartrate-resistant acid phosphatase activity, a marker enzyme for osteoclasts. This activity was increased by 1,25-dihydroxyvitamin D3 and parathyroid hormone, and calcitonin inhibited the increase in acid phosphatase activity stimulated by these compounds. Ultrastructurally, the multinucleated cells had several features similar to those of osteoclasts. These data suggest that the multinucleated cells in our culture have several characteristics of osteoclasts and that the potent bone-resorbing activity of 1,25-dihydroxyvitamin D3 in vivo and in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclasts.