Prostaglandin E2 induces expression of receptor activator of nuclear factor-κB ligand/osteoprotegrin ligand on pre-B cells:: Implications for accelerated osteoclastogenesis in estrogen deficiency
Prostaglandin E2 induces expression of receptor activator of nuclear factor-κB ligand/osteoprotegrin ligand on pre-B cells:: Implications for accelerated osteoclastogenesis in estrogen deficiency
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DOI：
10.1359/jbmr.2000.15.7.1321
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发表时间：
2000-07-01
影响因子：
6.2
通讯作者：
Yamada, Y
中科院分区：
文献类型：
--
作者：
Kanematsu, M;Sato, T;Yamada, Y
雌激素缺乏会加速破骨细胞的骨吸收，导致骨质流失。据报道，雌激素缺乏与小鼠骨髓中前 B 细胞数量的增加有关。本研究旨在阐明改变的 B 淋巴细胞生成和核因子 kappa B 配体 (RANKL) 受体激活剂（RANKL）（破骨细胞生成中的关键分子）在与雌激素缺乏相关的骨质流失中的作用。在前列腺素 E-2 (PGE(2)) 存在的情况下，来自卵巢切除 (OVX) 小鼠的骨髓细胞形成抗酒石酸酸性磷酸酶 (TRAP) 阳性破骨细胞样细胞的活性显着高于来自假手术小鼠的骨髓细胞。 Northern 印迹分析显示，PGE(2) 增加了骨髓细胞中 RANKL 信使 RNA (mRNA) 的数量，不仅是贴壁基质细胞，而且是非贴壁造血细胞；其中，OVX 小鼠中的 RANKL mRNA 比假手术小鼠更丰富，并且主要位于 B220(+) 细胞中。流式细胞术显示，骨髓中大多数B220(+)细胞为RANKL阳性，且OVX小鼠骨髓中RANKL阳性、B220(低)细胞的百分比高于假手术小鼠的骨髓。通过体内给予吲哚美辛，OVX小鼠中RANKL表达和这些细胞百分比的增加被消除。 PGE(2) 还显着增加小鼠前B 细胞系70Z/3 中RANKL mRNA 的水平和RANKL 蛋白的细胞表面表达。最后，通过事先去除B220(+)细胞，对PGE(2)的破骨反应显着降低，并且通过重新添加B220(+)细胞来恢复。结合雌激素缺乏时肿瘤坏死因子α（TNF-α）和白介素-1（IL-1）刺激的环加氧酶（COX）-2活性，这些结果表明，骨髓中B220（+）细胞数量的增加可能在雌激素缺乏时加速骨吸收中发挥重要作用，因为B220（+）细胞在雌激素缺乏时在细胞表面表现出RANKL。 PGE(2) 的存在，从而导致破骨细胞生成加速。
Estrogen deficiency causes bone loss as a result of accelerated osteoclastic bone resorption. It also has been reported that estrogen deficiency is associated with an increase in the number of pre-B cells in mouse bone marrow. The present study was undertaken to clarify the role of altered B lymphopoiesis and of the receptor activator of nuclear factor-kappa B ligand (RANKL), a key molecule in osteoclastogenesis, in the bone loss associated with estrogen deficiency. In the presence of prostaglandin E-2 (PGE(2)), the activity to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells was significantly greater in bone marrow cells derived from ovariectomized (OVX) mice than in those from sham-operated mice. Northern blot analysis revealed that PGE(2) increased the amount of RANKL messenger RNA (mRNA) in bone marrow cells, not only adherent stromal cells but nonadherent hematopoietic cells; among the latter, RANKL mRNA was more abundant in OVX mice than in sham-operated mice and was localized predominantly in B220(+) cells. Flow cytometry revealed that most B220(+) cells in bone marrow were RANKL positive and that the percentage of RANKL-positive, B220(low) cells was higher in bone marrow from OVX mice than in that from sham-operated mice. The increase in the expression of RANKL and the percentage of these cells in OVX mice was abolished by the administration of indomethacin in vivo. PGE(2) also markedly increased both the level of RANKL mRNA and cell surface expression of RANKL protein in the mouse pre-B cell line 70Z/3. Finally, osteoclastogenic response to PGE(2) was reduced markedly by prior depletion of B220(+) cells, and it was restored by adding back B220(+) cells. Taken together with stimulated cyclo-oxygenase (COX)-2 activity by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) in estrogen deficiency, these results suggest that an increase in the number of B220(+) cells in bone marrow may play an important role in accelerated bone resorption in estrogen deficiency because B220(+) cells exhibit RANKL on the cell surface in the presence of PGE(2), thereby leading to accelerated osteoclastogenesis.