RANKL inhibition improves bone properties in a mouse model of osteogenesis imperfecta.
RANKL inhibition improves bone properties in a mouse model of osteogenesis imperfecta.
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DOI：
10.3109/03008200903108472
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发表时间：
2010-04
影响因子：
2.9
通讯作者：
Pleshko N
中科院分区：
文献类型：
--
作者：
Bargman R;Huang A;Boskey AL;Raggio C;Pleshko N
近年来，一类新的靶向核因子-κB配体受体激活剂（RANKL）通路的药物被开发出来用于治疗骨质疏松症和其他骨疾病。在目前的研究中，我们对RANKL通路的抑制进行了评估，以评估对成骨不全（OI）动物模型oim/oim小鼠的“骨质量”和骨折发生率的影响。幼龄oim/oim（~6周龄）和野生型（+/+）小鼠分别用RANKL抑制剂（RANK-Fc）或生理盐水处理。治疗后，两种基因型的股骨骨密度均显著增加。在+/+小鼠中，股骨长度随着RANK-Fc的增加而减少。在oim/oim组中膈的几何测量显示，治疗组中ML骨膜和内膜直径以及AP皮质厚度增加。在+/+组中，ML皮质厚度和ML股骨膜直径随RANK-Fc显著增加。生物力学测试显示oim/oim和+/+小鼠的僵硬度增加。在+/+小鼠中，总菌株随着治疗而增加。组织学上，RANKL抑制导致两种基因型的生长板软骨保留。rank - fc处理的oim/oim小鼠的平均骨折次数与盐水处理的oim/oim小鼠相比没有显著减少。本临床前研究表明，在当前剂量下抑制RANKL可改善oim/oim骨的密度和一些几何和生物力学性能，但不能降低骨折发生率。需要进一步研究在更早的时间点开始治疗，以确定这种治疗模式是否在临床上对成骨不全症有用。
Recently, a new class of agents targeting the receptor activator of nuclear factor-κB ligand (RANKL) pathway has been developed for the treatment of osteoporosis and other bone diseases. In the current study, inhibition of the RANKL pathway was evaluated to assess effects on “bone quality” and fracture incidence in an animal model of osteogenesis imperfect (OI), the oim/oim mouse. Juvenile oim/oim (~6 weeks old) and wildtype (+/+) mice were treated with either a RANKL inhibitor (RANK-Fc) or saline. After treatment, bone density increased significantly in the femurs of both genotypes. Femoral length decreased with RANK-Fc in +/+ mice. Geometric measurements at mid-diaphysis in the oim/oim groups showed increases in the ML periosteal and endosteal diameters and AP cortical thickness in the treated groups. Within +/+ groups, ML cortical thickness and ML femoral periosteal diameter were significantly increased with RANK-Fc. Biomechanical testing revealed increased stiffness in oim/oim and +/+ mice. Total strain was increased with treatment in the +/+ mice. Histologically, RANKL inhibition resulted in retained growth plate cartilage in both genotypes. The average number of fractures sustained by RANK-Fc-treated oim/oim mice was not significantly decreased compared to saline treated oim/oim mice. This preclinical study demonstrated that RANKL inhibition at the current dose improved density and some geometric and biomechanical properties of oim/oim bone, but it did not decrease fracture incidence. Further studies that address commencement of therapy at earlier time points are needed to determine whether this mode of therapy will be clinically useful in OI.
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影响因子：
15.9
作者：
BONADIO, J;JEPSEN, KJ;GOLDSTEIN, SA
通讯作者：
GOLDSTEIN, SA
影响因子：
3.4
作者：
Madenci, E;Yilmaz, K;Coskun, Y
通讯作者：
Coskun, Y
DOI：
10.2106/00004623-197153070-00020
发表时间：
1971-01-01
影响因子：
5.3
作者：
ALBRIGHT, JA;GRUNT, JA
通讯作者：
GRUNT, JA
影响因子：
4.2
作者：
Camacho, NP;Raggio, CL;Boskey, AL
通讯作者：
Boskey, AL
影响因子：
5.8
作者：
Bone, Henry G.;Bolognese, Michael A.;Martin, Javier San
通讯作者：
Martin, Javier San