Orthopedics, Department of Clinical and Experimental Medicine, Faculty of Medicine, Linköping University, Linköping, Sweden.
J Bone Miner Res. 2010 Nov;25(11):2412-8. doi: 10.1002/jbmr.135.
Sclerostin is the product of the SOST gene. Loss-of-function mutations in the SOST gene result in a high-bone-mass phenotype, demonstrating that sclerostin is a negative regulator of bone mass. Primarily expressed by osteocytes in bone, sclerostin is reported to bind the LRP5/6 receptor, thereby antagonizing canonical Wnt signaling and negatively regulating bone formation. We therefore investigated whether systemic administration of a sclerostin-neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats. Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks. In four groups, the screws were tested for pull-out strength. At the time of euthanasia, a similar screw also was inserted in the contralateral tibia and pull-out tested immediately. Sclerostin antibody significantly increased the pull-out force by almost 50% compared with controls after 2 and 4 weeks. Also, the screws inserted at the time of euthanasia showed increased pull-out force. Micro-computed tomography (µCT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw. There also was a general increase in trabecular thickness in cancellous bone. Thus, as measured by the amount of bone and its mechanical resistance, the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone.
骨硬化蛋白是 SOST 基因的产物。SOST 基因的功能丧失性突变导致骨量高的表型，表明骨硬化蛋白是骨量的负调节剂。骨硬化蛋白主要由骨细胞表达，据报道它与 LRP5/6 受体结合，从而拮抗经典 Wnt 信号通路并负调控骨形成。因此，我们研究了全身性给予骨硬化蛋白中和抗体是否会增加大鼠创伤性干骺端骨的再生。年轻雄性大鼠的胫骨近端插入一根螺钉，并分为六组，每周两次皮下给予 25mg/kg 的骨硬化蛋白抗体或对照 2 或 4 周。在四组中，测试螺钉的拔出强度。在安乐死时，在对侧胫骨中也插入了类似的螺钉，并立即进行拔出测试。与对照组相比，骨硬化蛋白抗体在 2 周和 4 周后分别使拔出力增加了近 50%。此外，在安乐死时插入的螺钉显示出增加的拔出力。对其余两组的 micro-CT（µCT）进行分析显示，抗体使螺钉周围区域的骨体积分数增加了 30%。松质骨的小梁厚度也普遍增加。因此，根据骨量及其机械阻力的大小，骨硬化蛋白抗体增加了干骺端修复期间的骨形成，也增加了未受创伤的骨的骨形成。
