Guorui Cao, La Li, Shiqi Xiang, Hang Lin, Fuxing Pei, Rocky Sung Chi Tuan, Peter G Alexander
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引用次数: 0
Abstract
Background: Muscle injury and concomitant bone injury are important drivers to induce heterotopic ossification (HO). However, the related roles of muscle and concomitant bone injury in HO formation are still unclear. This study aims to develop a mouse model through the combination of hindlimb amputation (Am) and cardiotoxin (CTX) injection to investigate the mechanism of HO formation.
Method: The mice were randomly divided into Am group (Am of right hindlimb, n = 12), CTX group (CTX injection in the calf muscle of left hindlimb, n = 12) and Am + CTX group (the combination of Am of right hindlimb and CTX injection of left hindlimb, n = 18). MicroCT was used to evaluate the incidence of HO. Histology was used to investigate the progression of HO.
Results: The MicroCT showed that only Am or CTX injection failed to induce HO while the combination of Am and CTX injection successfully induced HO. The incidence of HO was significant in Am + CTX group on day 7 (0% vs 0% vs 83.3%, p = 0.001) and day 14 (0% vs 0% vs 83.3%, p = 0.048). HO was located on the left hindlimb where CTX was injected. Moreover, the bone volume and bone density on day 14 were higher than those on day 7 in Am + CTX group. Histology revealed the evidence of calcification and expression of osteogenic markers in calcification sites in Am + CTX group.
Conclusion: In summary, the combination of Am and CTX injection could successfully induce dystrophic calcification/HO, which occurs in the location of muscle injury.
背景:肌肉损伤和伴随的骨损伤是诱发异位骨化(HO)的重要驱动因素。然而，肌肉和伴随的骨损伤在HO形成中的相关作用尚不清楚。本研究拟通过后肢截肢(Am)联合心肌毒素(CTX)注射建立小鼠模型，探讨HO的形成机制。方法:将小鼠随机分为Am组(右后肢Am, n = 12)、CTX组(左后肢小腿肌注射CTX, n = 12)和Am + CTX组(右后肢Am与左后肢CTX联合注射，n = 18)。采用MicroCT评估HO的发生率。组织学检查HO的进展情况。结果:MicroCT显示Am或CTX均不能诱导HO, Am和CTX联合诱导HO成功。Am + CTX组HO发病率在第7天(0% vs 0% vs 83.3%， p = 0.001)和第14天(0% vs 0% vs 83.3%， p = 0.048)均有显著性差异。HO位于左后肢注射CTX处。Am + CTX组第14天的骨体积和骨密度高于第7天。Am + CTX组组织学显示钙化及钙化部位成骨标志物的表达。结论:综上所述，Am与CTX联合注射可成功诱导肌损伤部位的营养不良性钙化/HO。
期刊介绍：
Journal of Orthopaedic Surgery is an open access peer-reviewed journal publishing original reviews and research articles on all aspects of orthopaedic surgery. It is the official journal of the Asia Pacific Orthopaedic Association.
The journal welcomes and will publish materials of a diverse nature, from basic science research to clinical trials and surgical techniques. The journal encourages contributions from all parts of the world, but special emphasis is given to research of particular relevance to the Asia Pacific region.
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