Bateman T A, Dunstan C R, Ferguson V L, Lacey D L, Ayers R A, Simske S J
BioServe Space Technologies, University of Colorado, Boulder, CO 80309-0429, USA.
Bone. 2000 May;26(5):443-9. doi: 10.1016/S8756-3282(00)00256-8.
Osteoprotegerin (OPG) is a recently discovered protein related to the tumor necrosis factor receptor family. It has been shown to inhibit ovariectomy (ovx)-induced resorption in rats and increase bone mineral density in young mice. Tail suspension is a procedure that inhibits bone formation in maturing rodents. This study was designed to quantify OPG's effect on cortical bone formation. Fifty-four mice were assigned to one of five groups (n = 10-11/group). A baseline control group was killed on day 0 of the 10 day study. The remaining groups were: vivarium housed (nonsuspended) control mice receiving 0.3 mg/kg per day OPG; vivarium control mice receiving daily placebo injections; tail-suspended mice receiving 0. 3 mg/kg per day OPG; and tail-suspended mice receiving placebo injections. Tetracycline was administered on days 0 and 8. OPG treatment of tail-suspended mice produced mechanical properties similar to those of placebo-treated, vivarium-housed mice: structural stiffness (8.5%, 20.7%) and elastic (13.9%, 10.1%) and maximum (4.7%, 8.1%) force were increased compared with placebo controls (vivarium, suspended groups). Percent mineral composition was highly significantly greater (p < 0.001 for all comparisons) for OPG-treated mice in the femur, tibia, and humerus, relative to placebo treatment. Matrix mass was also significantly increased in the femur, although not to the same degree as mineral mass. OPG decreased the amount of femoral endocortical resorption compared with the placebo-treated groups for both vivarium (27%) and suspended (24%) mice. Administration of OPG significantly decreased endocortical formation of the tibia. Periosteal bone formation rates were not altered by OPG. OPG-mitigated tail suspension induced osteopenia not by returning bone formation to normal levels, but by inhibiting resorption and increasing percent mineral composition.
骨保护素（OPG）是一种最近发现的与肿瘤坏死因子受体家族相关的蛋白质。研究表明，它可抑制大鼠卵巢切除（ovx）诱导的骨吸收，并增加幼龄小鼠的骨矿物质密度。尾部悬吊是一种抑制成熟啮齿动物骨形成的方法。本研究旨在量化OPG对皮质骨形成的影响。54只小鼠被分为五组之一（每组n = 10 - 11只）。在为期10天的研究的第0天处死一个基线对照组。其余组为：饲养在动物饲养室（未悬吊）的对照小鼠，每天接受0.3 mg/kg的OPG；饲养在动物饲养室的对照小鼠，每天接受安慰剂注射；尾部悬吊的小鼠，每天接受0.3 mg/kg的OPG；以及尾部悬吊的小鼠，接受安慰剂注射。在第0天和第8天给予四环素。对尾部悬吊小鼠进行OPG治疗产生的力学性能与接受安慰剂治疗、饲养在动物饲养室的小鼠相似：与安慰剂对照组（饲养在动物饲养室、悬吊组）相比，结构刚度（分别增加8.5%、20.7%）、弹性力（分别增加13.9%、10.1%）和最大力（分别增加4.7%、8.1%）均有所增加。相对于安慰剂治疗，接受OPG治疗的小鼠在股骨、胫骨和肱骨中的矿物质组成百分比显著更高（所有比较的p < 0.001）。股骨中的基质质量也显著增加，尽管增加程度不如矿物质质量。与安慰剂治疗组相比，对于饲养在动物饲养室（减少27%）和悬吊（减少24%）的小鼠，OPG均减少了股骨干内侧皮质骨的吸收量。给予OPG显著降低了胫骨的干内侧皮质骨形成。OPG未改变骨膜骨形成率。OPG减轻尾部悬吊诱导的骨质减少，并非通过使骨形成恢复到正常水平，而是通过抑制骨吸收和增加矿物质组成百分比来实现。
