TY - JOUR
T1 - Acetabular Reaming Is a Reliable Model to Produce and Characterize Periarticular Heterotopic Ossification of the Hip
AU - Negri, Stefano
AU - Wang, Yiyun
AU - Li, Zhao
AU - Qin, Qizhi
AU - Lee, Seungyong
AU - Cherief, Masnsen
AU - Xu, Jiajia
AU - Tower, Robert Joel
AU - Presson, Bradley
AU - Levin, Adam
AU - McCarthy, Edward
AU - Levi, Benjamin
AU - James, Aaron W.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - PDGFR
KW - heterotopic bone
KW - hip arthroplasty
KW - myositis ossificans
KW - scleraxis
UR - http://www.scopus.com/inward/record.url?scp=85136407406&partnerID=8YFLogxK
U2 - 10.1093/stcltm/szac042
DO - 10.1093/stcltm/szac042
M3 - Article
C2 - 35758541
AN - SCOPUS:85136407406
SN - 2157-6564
VL - 11
SP - 876
EP - 888
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 8
ER -