Morse A, Yu N Y C, Peacock L, Mikulec K, Kramer I, Kneissel M, McDonald M M, Little D G
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia.
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, Australia.
Bone. 2015 Feb;71:155-63. doi: 10.1016/j.bone.2014.10.018. Epub 2014 Oct 30.
Sclerostin deficiency, via genetic knockout or anti-Sclerostin antibody treatment, has been shown to cause increased bone volume, density and strength of calluses following endochondral bone healing. However, there is limited data on the effect of Sclerostin deficiency on the formative early stage of fibrocartilage (non-bony tissue) formation and removal. In this study we extensively investigate the early fibrocartilage callus. Closed tibial fractures were performed on Sost(-/-) mice and age-matched wild type (C57Bl/6J) controls and assessed at multiple early time points (7, 10 and 14days), as well as at 28days post-fracture after bony union. External fixation was utilized, avoiding internal pinning and minimizing differences in stability stiffness, a variable that has confounded previous research in this area. Normal endochondral ossification progressed in wild type and Sost(-/-) mice with equivalent volumes of fibrocartilage formed at early day 7 and day 10 time points, and bony union in both genotypes by day 28. There were no significant differences in rate of bony union; however there were significant increases in fibrocartilage removal from the Sost(-/-) fracture calluses at day 14 suggesting earlier progression of endochondral healing. Earlier bone formation was seen in Sost(-/-) calluses over wild type with greater bone volume at day 10 (221%, p<0.01). The resultant Sost(-/-) united bony calluses at day 28 had increased bone volume fraction compared to wild type calluses (24%, p<0.05), and the strength of the fractured Sost(-/-) tibiae was greater than that that of wild type fractured tibiae. In summary, bony union was not altered by Sclerostin deficiency in externally-fixed closed tibial fractures, but fibrocartilage removal was enhanced and the resultant united bony calluses had increased bone fraction and increased strength.
通过基因敲除或抗硬化蛋白抗体治疗导致的硬化蛋白缺乏，已被证明可使软骨内骨愈合后骨痂的骨体积、密度和强度增加。然而，关于硬化蛋白缺乏对纤维软骨（非骨组织）形成和清除的早期形成阶段的影响的数据有限。在本研究中，我们广泛研究了早期纤维软骨骨痂。对Sost（-/-）小鼠和年龄匹配的野生型（C57Bl/6J）对照进行闭合性胫骨骨折，并在多个早期时间点（7、10和14天）以及骨折后28天骨愈合后进行评估。采用外固定，避免内固定，并尽量减少稳定性刚度的差异，这一变量在该领域以前的研究中造成了混淆。野生型和Sost（-/-）小鼠的软骨内骨化正常进行，在第7天和第10天早期形成的纤维软骨体积相当，两种基因型在第28天均实现骨愈合。骨愈合速率没有显著差异；然而，在第14天，Sost（-/-）骨折骨痂中的纤维软骨清除显著增加，表明软骨内愈合进程较早。与野生型相比，Sost（-/-）骨痂中可见更早的骨形成，在第10天骨体积更大（221%，p<0.01）。与野生型骨痂相比，第28天形成的Sost（-/-）联合骨痂的骨体积分数增加（24%，p<0.05），并且Sost（-/-）骨折胫骨的强度大于野生型骨折胫骨。总之，在外部固定的闭合性胫骨骨折中，硬化蛋白缺乏不会改变骨愈合，但会增强纤维软骨清除，并且形成的联合骨痂的骨分数增加，强度增加。
