Centre for Blast Injury Studies, Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
Centre for Blast Injury Studies, Department of Bioengineering, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
Bone. 2021 Feb;143:115765. doi: 10.1016/j.bone.2020.115765. Epub 2020 Dec 4.
Heterotopic ossification (HO) is the process of de novo bone formation in non-osseous tissues. HO can occur following trauma and burns and over 60% of military personnel with blast-associated amputations develop HO. This rate is far higher than in other trauma-induced HO development. This suggests that the blast effect itself is a major contributing factor, but the pathway triggering HO following blast injury specifically is not yet fully identified. Also, because of the difficulty of studying the disease using clinical data, the only sources remain the relevant in vivo models. The aim of this paper is first to review the key biomarkers and signalling pathways identified in trauma and blast induced HO in order to summarize the molecular mechanisms underlying HO development, and second to review the blast injury in vivo models developed. The literature derived from trauma-induced HO suggests that inflammatory cytokines play a key role directing different progenitor cells to transform into an osteogenic class contributing to the development of the disease. This highlights the importance of identifying the downstream biomarkers under specific signalling pathways which might trigger similar stimuli in blast to those of trauma induced formation of ectopic bone in the tissues surrounding the site of the injury. The lack of information in the literature regarding the exact biomarkers leading to blast associated HO is hampering the design of specific therapeutics. The majority of existing blast injury in vivo models do not fully replicate the combat scenario in terms of blast, fracture and amputation; these three usually happen in one insult. Hence, this paper highlights the need to replicate the full effect of the blast in preclinical models to better understand the mechanism of blast induced HO development and to enable the design of a specific therapeutic to supress the formation of ectopic bone.
异位骨化（HO）是指在非骨组织中形成新骨的过程。HO 可在创伤和烧伤后发生，超过 60%的与爆炸相关截肢的军事人员会发生 HO。这一发生率远高于其他创伤性 HO 发展。这表明爆炸效应本身是一个主要因素，但具体导致爆炸损伤后 HO 的途径尚未完全确定。此外，由于使用临床数据研究该疾病存在困难，唯一的来源仍然是相关的体内模型。本文的目的首先是回顾创伤和爆炸诱导的 HO 中确定的关键生物标志物和信号通路，以总结 HO 发展的分子机制，其次是回顾开发的爆炸损伤体内模型。创伤诱导的 HO 相关文献表明，炎症细胞因子在指导不同祖细胞转化为成骨细胞类，从而导致疾病发展方面发挥着关键作用。这突出表明，必须确定特定信号通路下的下游生物标志物，这些生物标志物可能在爆炸中引发与创伤类似的刺激，从而在损伤部位周围的组织中形成异位骨。文献中缺乏关于导致爆炸相关 HO 的确切生物标志物的信息，这阻碍了特定治疗方法的设计。大多数现有的爆炸损伤体内模型在爆炸、骨折和截肢方面都不能完全复制战斗场景；这三种情况通常同时发生。因此，本文强调需要在临床前模型中复制爆炸的全部效应，以更好地理解爆炸诱导的 HO 发展机制，并能够设计出一种特定的治疗方法来抑制异位骨的形成。
