Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Orthopaedic and Trauma Surgery Unit, Department of Surgery, Dentistry, Paediatrics and Gynaecology of the University of Verona, Verona, Italy.
Stem Cells Transl Med. 2022 Aug 23;11(8):876-888. doi: 10.1093/stcltm/szac042.
Heterotopic ossification (HO) is a pathologic process characterized by the formation of bone tissue in extraskeletal locations. The hip is a common location of HO, especially as a complication of arthroplasty. Here, we devise a first-of-its-kind mouse model of post-surgical hip HO and validate expected cell sources of HO using several HO progenitor cell reporter lines. To induce HO, an anterolateral surgical approach to the hip was used, followed by disclocation and acetabular reaming. Animals were analyzed with high-resolution roentgenograms and micro-computed tomography, conventional histology, immunohistochemistry, and assessments of fluorescent reporter activity. All the treated animals' developed periarticular HO with an anatomical distribution similar to human patients after arthroplasty. Heterotopic bone was found in periosteal, inter/intramuscular, and intracapsular locations. Further, the use of either PDGFRα or scleraxis (Scx) reporter mice demonstrated that both cell types gave rise to periarticular HO in this model. In summary, acetabular reaming reproducibly induces periarticular HO in the mouse reproducing human disease, and with defined mesenchymal cellular contributors similar to other experimental HO models. This protocol may be used in the future for further detailing of the cellular and molecular mediators of post-surgical HO, as well as the screening of new therapies.
异位骨化(HO)是一种以骨骼组织在骨骼外位置形成为特征的病理过程。髋关节是 HO 的常见部位,尤其是作为关节置换术的并发症。在这里,我们设计了一种首例用于术后髋关节 HO 的小鼠模型,并使用几种 HO 祖细胞报告系验证了预期的 HO 细胞来源。为了诱导 HO,采用髋关节前外侧手术入路,随后脱位和髋臼扩孔。通过高分辨率射线照相和微计算机断层扫描、常规组织学、免疫组织化学以及荧光报告基因活性评估对动物进行分析。所有接受治疗的动物均出现了与人工关节置换术后人类患者相似的关节周围 HO,其解剖分布与人类患者相似。异位骨在骨膜、肌间/肌内和关节囊内位置均可发现。此外,使用 PDGFRα 或 Scleraxis(Scx)报告小鼠表明,这两种细胞类型在该模型中均能产生关节周围 HO。总之,髋臼扩孔可在小鼠中重现诱导关节周围 HO,重现人类疾病,并具有与其他实验性 HO 模型相似的明确间充质细胞贡献者。该方案将来可用于进一步详细研究术后 HO 的细胞和分子介质,以及筛选新的治疗方法。