Effects of prostaglandins on human hematopoietic osteoclast precursors
Effects of prostaglandins on human hematopoietic osteoclast precursors
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DOI：
10.1210/en.138.4.1476
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发表时间：
1997-04-01
期刊：
影响因子：
4.8
通讯作者：
deVernejoul, MC
中科院分区：
文献类型：
--
作者：
Roux, S;Pichaud, F;deVernejoul, MC
前列腺素E（2）（PGE（2））对破骨细胞（OC）分化的影响尚不清楚，根据所用的体外系统，可能是刺激剂或抑制剂。这可能反映了通过中间细胞的间接机制。我们研究了PGE（2）在无基质细胞的情况下对人脐带血单核细胞（CBMs）向OC分化的直接作用。在1，25-二羟维生素D-3刺激的CBM培养物中形成类似OC的巨噬细胞和多核细胞（MNC）。在本研究中，如前所述，在存在或不存在PGE的情况下培养CBM 3周（2）。在PGE（2）的存在下，MNC的数量显著减少，在第7天评估的培养的CBM的增殖也是如此。进行免疫组织化学以评价巨噬细胞标志物（CD 11b和CD 14）和OC标志物（β（3）-链）。PGE（2）显著增加CD 11b和CD 14阳性细胞的数量，而β（3）链阳性细胞的数量显著减少。用从培养的CBM中提取的RNA通过逆转录-PCR评价β（3）-链、c-fos和人降钙素受体（h-CTR）信使RNA（mRNA）的表达。在PGE（2）存在下，β（3）链和c-fos mRNA的表达从培养的第一周开始减少。h-CTR mRNA表达也降低，在PGE存在下仅检测到h-CTR 1亚型（2）。此外，当仅在培养的最后一周加入PGE（2）时，当没有发生CBM增殖时，与对照培养物相比，CD 11b和β（3）阳性细胞的数量没有变化，MNCs的比例、融合指数和c-fos mRNA的表达也没有变化。总之，我们的结果表明PGE（2）对人OC从CBM分化具有抑制作用，可能通过减少这些培养物中的前体增殖。我们还假设PGE（2）可能通过增加分化为巨噬细胞的前体细胞的比例来减少OC的分化。此外，这可能是抑制c-fos表达的结果。
The effect of prostaglandin E(2) (PGE(2)) on osteoclast (OC) differentiation is unclear, either stimulator or inhibitor, depending on the in vitro system used. This probably reflects indirect mechanisms through intermediate cells. We have investigated the direct effect of PGE(2) on human OC differentiation from cord blood monocytes (CBMs) in the absence of stromal cells. Macrophages and multinucleated cells (MNCs) resembling OCs form in cultures of CBMs stimulated by 1,25-dihydroxyvitamin D-3. In the present study, CBMs were cultured for 3 weeks, as previously described, in the presence or absence of PGE(2). The number of MNCs was significantly reduced in the presence of PGE(2) as was the proliferation of cultured CBMs, assessed on day 7. Immunohistochemistry was performed to evaluate macrophage markers (CD11b and CD14) and OC marker (beta(3)-chain). PGE(2) significantly increased the numbers of CD11b-positive and CD14-positive cells, whereas the number of beta(3)-chain-positive cells was significantly decreased. beta(3)-Chain, c-fos, and human calcitonin receptor (h-CTR) messenger RNA (mRNA) expressions were evaluated by reverse transcription-PCR with RNA extracted from cultured CBMs. In the presence of PGE(2), expression of beta(3)-chain and c-fos mRNA was reduced from the first week of culture. h-CTR mRNA expression was also reduced, and only the h-CTR1 isoform was detected in the presence of PGE(2). In addition, when PGE(2) was added only during the last week of culture, when no CBM proliferation occurred, the number of CD11b- and beta(3)-positive cells was unchanged compared to that in the control culture, as were the proportion of MNCs, the fusion index, and the expression of c-fos mRNA.In conclusion, our results suggest that PGE(2) has an inhibitory effect on human OC differentiation from CBMs, possibly by reducing precursor proliferation in these cultures. We also hypothesize that PGE(2) may reduce OC differentiation by increasing the proportion of precursor cells that differentiate into macrophages. In addition, this may be the result of inhibition of the c-fos expression in CBMs.