Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women.
Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women.
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DOI：
10.1016/j.bone.2011.04.015
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发表时间：
2011-08
期刊：
影响因子：
4.1
通讯作者：
Khosla, Sundeep
中科院分区：
文献类型：
--
作者：
Moedder, Ulrike I.;Roforth, Matthew M.;Hoey, Kelley;McCready, Louise K.;Peterson, James M.;Monroe, David G.;Oursler, Merry Jo;Khosla, Sundeep
雌激素水平的降低不仅导致绝经后早期骨丢失，而且还导致随着年龄的增长骨丢失。虽然雌激素对维持骨形成至关重要，但这种作用的机制仍不清楚。因此，我们评估了4个月的经皮雌二醇治疗（0.05 mg/天）与未治疗（每组n = 16）相比，对绝经后妇女新鲜分离的骨髓骨祖细胞（造血谱系[lin]-/Stro 1+）中预先指定途径的基因表达的影响。我们还评估了雌激素治疗是否调节Wnt拮抗剂、硬化蛋白和DKK 1以及5-羟色胺、OPG、RANKL、脂联素、催产素和炎性细胞因子（TNFα、IL-1β、IL-6）的外周血或骨髓血浆水平，因为这些分子中的每一种最近已被证明在调节成骨细胞功能和/或对雌激素反应中起重要作用。我们观察到，与对照组相比，雌激素治疗组的骨髓lin-/Stro 1+细胞中几种增殖标志物（细胞周期蛋白B1、细胞周期蛋白E1、E2 F1）的表达显著降低，粘附分子（N-钙粘蛋白）增加。两组之间的外周血或骨髓血浆标记物水平无差异，除了硬化蛋白水平，其在雌激素治疗组中显著低于对照组妇女外周血清（32%，P = 0.009）和骨髓血浆（34%，P = 0.017）。骨髓与外周血浆中几个因素的水平存在显著差异：骨髓中的硬化素和OPG水平高于外周血浆，而外周中的5-羟色胺和脂联素水平高于骨髓血浆。总之，我们的数据直接评估了雌激素对人类骨祖细胞的可能调节，表明与先前在小鼠中的研究一致，雌激素抑制了人骨髓lin-/Stro 1+细胞的增殖，这可能代表了早期骨祖细胞。需要进一步的动物和人类研究来确定我们在这些细胞中粘附分子的mRNA中观察到的变化以及在骨中局部sclerostin产生中观察到的变化在介导雌激素对人类骨代谢的影响中的作用。
Decreases in estrogen levels contribute not only to early postmenopausal bone loss but also to bone loss with aging. While estrogen is critical for the maintenance of bone formation, the mechanism(s) of this effect remain unclear. Thus, we assessed the effects of 4 months of transdermal estradiol treatment (0.05 mg/day) of postmenopausal women as compared to no treatment (n = 16 per group) on the expression of genes in pre-specified pathways in freshly isolated bone marrow osteoprogenitor cells (hematopoietic lineage [lin]−/Stro1+). We also evaluated whether estrogen treatment modulated peripheral blood or bone marrow plasma levels of the Wnt antagonists, sclerostin and DKK1, as well as serotonin, OPG, RANKL, adiponectin, oxytocin, and inflammatory cytokines (TNFα, IL-1β, IL-6), as each of these molecules have recently been shown to play an important role in regulating osteoblast function and/or being responsive to estrogen. We observed a significant decrease in the expression of several proliferation markers (cyclin B1, cyclin E1, E2F1) and increase in adhesion molecules (N-cadherin) in bone marrow lin−/Stro1+ cells from estrogen-treated compared to control women. None of the peripheral blood or bone marrow plasma marker levels differed between the two groups, with the exception of sclerostin levels, which were significantly lower in the estrogen-treated as compared to the control women in peripheral serum (by 32%, P = 0.009) and in bone marrow plasma (by 34%, P = 0.017). There were significant differences in bone marrow versus peripheral plasma levels of several factors: sclerostin and OPG levels were higher in bone marrow as compared to peripheral plasma, whereas serotonin and adiponectin levels were higher in peripheral as compared to bone marrow plasma. In summary, our data directly assessing possible regulation by estrogen of osteoprogenitor cells in humans indicate that, consistent with previous studies in mice, estrogen suppresses the proliferation of human bone marrow lin−/Stro1+ cells, which likely represent early osteoprogenitor cells. Further animal and human studies are needed to define the role of the changes we observed in mRNAs for adhesion molecules in these cells and in local sclerostin production in bone in mediating the effects of estrogen on bone metabolism in humans.
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