Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats
Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats
复制标题
DOI：
10.1113/expphysiol.2006.033217
复制
发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Saffar, JL
中科院分区：
文献类型：
--
作者：
Lesclous, P;Schramm, F;Saffar, JL
短期研究表明，组胺通过其H-2受体（H2R）参与调节卵巢切除（OVX）大鼠长骨中小梁骨丢失的介质网络。目前尚不清楚组胺的这种作用是否会随着时间的推移而持续或涉及其他骨骼部位。在这项研究中，大鼠在OVX后维持6个月，每天接受生理盐水或法莫替丁（10 mg kg（-1））（一种H2 R拮抗剂）治疗。在实验期结束时，无论是否给予法莫替丁治疗，OVX大鼠的股骨骨小梁质量均显著降低。相反，在第四腰椎中，骨丢失开始晚于股骨，法莫替丁治疗减弱了骨小梁体积的下降，保护了骨小梁结构，保持了皮质厚度，减少了破骨细胞和抗酒石酸酸性磷酸酶阳性破骨细胞的数量，而对骨形成参数没有影响。在OVX大鼠的脊椎骨髓中，肥大细胞（MC）和非MC组胺产生细胞的数量增加，而法莫替丁治疗显着减少这两个细胞群。这些数据表明，H2R拮抗作用不会长期保护骨小梁质量，短期保护作用涉及所有骨骼。组胺是参与早期阶段的强骨吸收，但不是在晚期阶段的缓慢吸收，这表明不同的介质网络控制的两个阶段的破坏。组胺可能是介导早期阶段的网络的一部分。
Short-term studies have shown that histamine is involved, via its H-2 receptors (H2R), in the mediator network regulating trabecular bone loss in long bones of ovariectomized (OVX) rats. It is not known whether this effect of histamine persists over time or involves other skeletal sites. In this study, rats were maintained for 6 months postOVX and treated daily with saline or famotidine (10 mg kg(-1)), an H2R antagonist. At the end of the experimental period, femur trabecular bone mass was markedly decreased in OVX rats, whether or not they were treated with famotidine. In contrast, in the fourth lumbar vertebra, where bone loss starts later than in the femur, famotidine treatment attenuated the decline in trabecular bone volume, protected the trabecular architecture, maintained the thickness of the cortices and reduced the numbers of osteoclasts and tartrate-resistant acid phosphatase-positive preosteoclasts, whereas it had no influence on bone formation parameters. In vertebral bone marrow of OVX rats, the numbers of mast cells (MCs) and non-MC histamine-producing cells increased, while famotidine treatment significantly diminished both cell populations. These data show that H2R antagonism does not protect trabecular bone mass in the long term, and that short-term protection involves all bones. Histamine is involved during the early phase of strong osteoclastic resorption but not during the late phase of slower resorption, suggesting that different mediator networks control the two phases of destruction. Histamine would be part of the network mediating the early phase.