TY - JOUR
T1 - Characterization of cells isolated from genetic and trauma-induced heterotopic ossification
AU - Agarwal, Shailesh
AU - Drake, James
AU - Qureshi, Ammar T.
AU - Loder, Shawn
AU - Li, Shuli
AU - Shigemori, Kay
AU - Peterson, Jonathan
AU - Cholok, David
AU - Forsberg, Jonathan A.
AU - Mishina, Yuji
AU - Davis, Thomas A.
AU - Levi, Benjamin
N1 - Funding Information:
SA is funded by the NIH Loan Repayment Program, Plastic Surgery Foundation, Coller Society, NIH F32 AR066499. JD is funded by HHMI Medical Fellows Program. SL (Loder) is funded by HHMI Medical Fellows Program. BL is funded by 1K08GM109105-0, Plastic Surgery Foundation National Endowment Award, American Association of Plastic Surgery Research Fellowship, Association for Academic Surgery Roslyn Award, American Association for the Surgery of Trauma Research and Education Foundation Scholarship, and DOD: W81XWH-14-DMRDP-CRMRP-NMSIRA. YM is funded by NIH R01DE020843, DoD W81XWH-11-2-0073. JAF is funded by CDMRP (W81XWH-13-2-0077; PI-JAF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Department of Defense requires that we include the following in addition: "Some of the authors are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. ?105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C ?101 defined a U.S. Government work as a work prepared by a military service member or employees of the U.S. Government as part of that person's official duties. The opinions or assertions contained in this paper are the private views of the authors and are not to be construed as reflecting the views, policy or positions of the Department of the Navy, Department of Defense nor the U.S. Government."
Publisher Copyright:
© 2016, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2016/8
Y1 - 2016/8
N2 - Heterotopic ossification (HO) is the pathologic formation of bone separate from the normal skeleton. Although several models exist for studying HO, an understanding of the common in vitro properties of cells isolated from these models is lacking. We studied three separate animal models of HO including two models of trauma-induced HO and one model of genetic HO, and human HO specimens, to characterize the properties of cells derived from tissue containing pre-and mature ectopic bone in relation to analogous mesenchymal cell populations or osteoblasts obtained from normal muscle tissue. We found that when cultured in vitro, cells isolated from the trauma sites in two distinct models exhibited increased osteogenic differentiation when compared to cells isolated from uninjured controls. Furthermore, osteoblasts isolated from heterotopic bone in a genetic model of HO also exhibited increased osteogenic differentiation when compared with normal osteoblasts. Finally, osteoblasts derived from mature heterotopic bone obtained from human patients exhibited increased osteogenic differentiation when compared with normal bone from the same patients. These findings demonstrate that across models, cells derived from tissues forming heterotopic ossification exhibit increased osteogenic differentiation when compared with either normal tissues or osteoblasts. These cell types can be used in the future for in vitro investigations for drug screening purposes.
AB - Heterotopic ossification (HO) is the pathologic formation of bone separate from the normal skeleton. Although several models exist for studying HO, an understanding of the common in vitro properties of cells isolated from these models is lacking. We studied three separate animal models of HO including two models of trauma-induced HO and one model of genetic HO, and human HO specimens, to characterize the properties of cells derived from tissue containing pre-and mature ectopic bone in relation to analogous mesenchymal cell populations or osteoblasts obtained from normal muscle tissue. We found that when cultured in vitro, cells isolated from the trauma sites in two distinct models exhibited increased osteogenic differentiation when compared to cells isolated from uninjured controls. Furthermore, osteoblasts isolated from heterotopic bone in a genetic model of HO also exhibited increased osteogenic differentiation when compared with normal osteoblasts. Finally, osteoblasts derived from mature heterotopic bone obtained from human patients exhibited increased osteogenic differentiation when compared with normal bone from the same patients. These findings demonstrate that across models, cells derived from tissues forming heterotopic ossification exhibit increased osteogenic differentiation when compared with either normal tissues or osteoblasts. These cell types can be used in the future for in vitro investigations for drug screening purposes.
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U2 - 10.1371/journal.pone.0156253
DO - 10.1371/journal.pone.0156253
M3 - Article
C2 - 27494521
AN - SCOPUS:84983456342
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0156253
ER -