Endogenous bone‐resorbing factors in estrogen deficiency: Cooperative effects of IL‐1 and IL‐6
Endogenous bone‐resorbing factors in estrogen deficiency: Cooperative effects of IL‐1 and IL‐6
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雌激素缺乏时的内源性骨吸收因子：IL-1 和 IL-6 的协同作用
DOI：
10.1002/jbmr.5650100914
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发表时间：
1995
影响因子：
6.2
通讯作者：
T. Suda
中科院分区：
文献类型：
--
作者：
C. Miyaura;Kenichiro Kusano;T. Masuzawa;O. Chaki;Y. Onoe;M. Aoyagi;Takahisa Sasaki;T. Tamura;Y. Koishihara;Y. Ohsugi;T. Suda
雌激素缺乏通过刺激破骨细胞骨吸收导致明显的骨质流失。为了探索雌激素缺乏中涉及的内源性骨吸收因子，我们检测了从卵巢切除（OVX）小鼠收集的小鼠骨髓上清中存在的骨吸收活性。在小鼠长骨器官培养中加入20-80%的骨髓上清液，剂量依赖性地刺激骨吸收。OVX小鼠骨髓上清液的内源性骨吸收活性在术后2-4周明显高于假手术小鼠，体外吲哚美辛显著降低。抗IL - 1α抗体完全中和OVX小鼠骨髓上清液中存在的骨吸收活性。针对IL - 1β、IL - 6和IL - 6受体的抗体也能部分中和它。ELISA法测定骨髓上清液中IL - 1α的浓度明显高于血清，但OVX前后IL - 1α浓度变化不明显。OVX小鼠骨髓上清液中IL - 1β的浓度低于检测限。OVX刺激骨髓上清液中的IL - 1活性，通过胸腺细胞的增殖来测量。然而，OVX小鼠骨髓上清液中的IL - 1α水平不足以刺激骨吸收。与血清浓度相比，骨髓上清液中IL - 6的含量也明显升高，OVX进一步提高了IL - 6的含量。然而，单独存在于OVX小鼠骨髓上清液中的IL - 6再次没有刺激骨吸收。同时加入IL‐1 （50 pg/ml）、IL‐6 （0.2 ng/ml）、sIL‐6受体（1 ng/ml）和PGE2 (7 ng/ml)，这相当于OVX小鼠骨髓上清液中的内源性浓度，共同诱导骨吸收。这些结果表明，雌激素缺乏时骨吸收的增强是由多种因素而不是单一因素引起的。
Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. To explore the endogenous bone‐resorbing factors involved in estrogen deficiency, we examined the bone‐resorbing activity present in the supernatant fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding bone marrow supernatants at 20–80% to organ cultures of mouse long bones dose‐dependently stimulated bone resorption. The endogenous bone‐resorbing activity present in bone marrow supernatants from OVX mice was much higher than that from sham‐operated mice 2–4 weeks after surgery, and it was significantly diminished by indomethacin in vitro. Anti‐IL‐1α antibody completely neutralized the bone‐resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL‐1β, IL‐6, and IL‐6 receptors also neutralized it, but partially. The concentration of IL‐1α measured by ELISA was much higher in bone marrow supernatants than in sera, but it was not appreciably changed before or after OVX. The concentration of IL‐1β in bone marrow supernatants from OVX mice was less than the detection limit. OVX stimulated IL‐1 activity in bone marrow supernatants measured by means of the proliferation of thymocytes. However, the level of IL‐1α present in bone marrow supernatants from OVX mice was insufficient to stimulate bone resorption. Compared with the serum concentration, bone marrow supernatants contained a much higher level of IL‐6 as well, and it was further increased by OVX. However, IL‐6 alone present in bone marrow supernatants from OVX mice again did not stimulate bone resorption. The concurrent addition of IL‐1 (50 pg/ml), IL‐6 (0.2 ng/ml), sIL‐6 receptor (1 ng/ml), and PGE2 (7 ng/ml), which equaled the endogenous concentrations in bone marrow supernatants from OVX mice, co‐operatively induced bone resorption. These results suggest that the enhanced bone resorption that occurs during estrogen deficiency is due to multi‐factors rather than to a single factor.
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DOI：
10.1073/pnas.88.7.2692
发表时间：
1991-04-01
影响因子：
11.1
作者：
XIE, WL;CHIPMAN, JG;SIMMONS, DL
通讯作者：
SIMMONS, DL
DOI：
10.1073/pnas.88.12.5134
发表时间：
1991-06-01
影响因子：
11.1
作者：
PACIFICI, R;BROWN, C;AVIOLI, LV
通讯作者：
AVIOLI, LV
影响因子：
15.9
作者：
KIMBLE, RB;VANNICE, JL;PACIFICI, R
通讯作者：
PACIFICI, R
环氧合酶相关基因的鉴定及其在前列腺素形成中的潜在作用。
DOI：
10.1016/0006-291x(89)91819-6
发表时间：
1989
影响因子：
3.1
作者：
Rosen,GD;Birkenmeier,TM;Raz,A;Holtzman,MJ
通讯作者：
Holtzman,MJ
DOI：
10.1073/pnas.89.11.4888
发表时间：
1992-06-01
影响因子：
11.1
作者：
OBANION, MK;WINN, VD;YOUNG, DA
通讯作者：
YOUNG, DA