Acetabular Reaming Is a Reliable Model to Produce and Characterize Periarticular Heterotopic Ossification of the Hip

• Published in: Stem cells translational medicine 2022-08, Vol.11 (8), p.876-888
• Main Authors: Negri, Stefano, Wang, Yiyun, Li, Zhao, Qin, Qizhi, Lee, Seungyong, Cherief, Masnsen, Xu, Jiajia, Hsu, Ginny Ching-Yun, Tower, Robert Joel, Presson, Bradley, Levin, Adam, McCarthy, Edward, Levi, Benjamin, James, Aaron W
• Format: Article
• Language: English
• Subjects: Animals; Arthroplasty - adverse effects; Arthroplasty, Replacement, Hip - adverse effects; Arthroplasty, Replacement, Hip - methods; Humans; Mesenchymal Stem Cells - pathology; Mice; Ossification, Heterotopic - pathology; Stem Cells - pathology; Tissue-Specific Progenitor and Stem Cells; X-Ray Microtomography - adverse effects
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1093/stcltm/szac042

Abstract 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. Graphical Abstract Heterotopic ossification (HO) of the hip was induced using an acetabular reaming model. 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 a portion of osteochondral cells in periarticular HO.