INTERLEUKIN-1 RECEPTOR ANTAGONIST AND TUMOR-NECROSIS-FACTOR BINDING-PROTEIN DECREASE OSTEOCLAST FORMATION AND BONE-RESORPTION IN OVARIECTOMIZED MICE
INTERLEUKIN-1 RECEPTOR ANTAGONIST AND TUMOR-NECROSIS-FACTOR BINDING-PROTEIN DECREASE OSTEOCLAST FORMATION AND BONE-RESORPTION IN OVARIECTOMIZED MICE
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DOI：
10.1172/jci117606
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发表时间：
1994-12-01
影响因子：
15.9
通讯作者：
PACIFICI, R
中科院分区：
文献类型：
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作者：
KITAZAWA, R;KIMBLE, RB;PACIFICI, R
为了研究IL-1、IL-6和TNF对雌激素缺乏诱导的破骨细胞生成增加的贡献，在手术后的前2周，用IL-1受体拮抗剂（IL-1 ra）（IL-1的竞争性抑制剂）、TNF结合蛋白（TNFbp）（TNF的抑制剂）或抗IL-6抗体（Ab）20 F3治疗卵巢切除（ovx）小鼠。ovx可增加骨髓细胞分泌IL-1和TNF，但不增加IL-6，并增加用1，25（OH）（2）D-3处理的骨髓培养物中TRAP阳性破骨细胞样多核细胞（MNCs）的形成。通过使用17 β雌二醇、IL-1 ra、TNFbp或抗IL-6 Ab进行体内治疗，可阻止ovx诱导的MNC形成增加。然而，由抗IL-6 Ab诱导的MNC形成的百分比变化在ovx和假手术动物中相似，而IL-1 ra和TNFbp仅在ovx小鼠中有效。在体外用IL-1 ra和TNFbp处理骨髓培养物也能减少MNC的形成，但用抗IL-6 Ab处理则无此作用。卵巢还增加了骨吸收在体内和体外，作为评估尿排泄的吡啶啉交联和形成的吸收坑，分别。IL-1 ra、TNFbp和雌激素在体内和体外均降低骨吸收，而抗IL-6 Ab在体外抑制骨吸收，但在体内不抑制骨吸收。总之，这些数据表明，IL-1和TNF在介导OVX对破骨细胞生成和骨吸收的影响中发挥直接作用。这些数据还表明，IL-6是不是必不可少的增加骨吸收在早期卵巢切除术期间。
To investigate the contribution of IL-1, IL-6, and TNF to the increased osteoclastogenesis induced by estrogen deficiency, ovariectomized (ovx) mice were treated with either IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1, TNF binding protein (TNFbp), an inhibitor of TNF, or the anti-IL-6 antibody (Ab) 20F3 for the first 2 wk after surgery. ovx increased the bone marrow cells secretion of IL-1 and TNF, but not IL-6, and the formation of TRAP-positive osteoclast-like multinucleated cells (MNCs) in bone marrow cultures treated with 1,25(OH)(2)D-3. The increase in MNC formation induced by ovx was prevented by in vivo treatment with either 17 beta estradiol, IL-1ra, TNFbp, or anti IL-6 Ab. However, the percent change in MNC formation induced by the anti-IL-6 Ab was similar in ovx and sham-operated animals, whereas IL-1ra and TNFbp were effective only in ovx mice. MNC formation was also decreased by in vitro treatment of bone marrow cultures with IL-1ra and TNFbp, but not with anti-IL-6 Ab. Ovx also increased bone resorption in vivo and in vitro, as assessed by the urinary excretion of pyridinoline cross links and the formation of resorption pits, respectively. IL-1ra, TNFbp and estrogen decreased bone resorption in vivo and in vitro whereas the anti-IL-6 Ab inhibited bone resorption in vitro but not in vivo. In conclusion, these data indicate that IL-1 and TNF play a direct role in mediating the effects of ovx on osteoclastogenesis and bone resorption. The data also suggest that IL-6 is not essential for increasing bone resorption in the early postovariectomy period.