title: Characterization of Cells Isolated from Genetic and Trauma-Induced Heterotopic Ossification.
abstract: 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.
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Shailesh
authors: S
authors: Agarwal
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: James
authors: J
authors: Drake
authors: Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
authors: Ammar T
authors: AT
authors: Qureshi
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Shawn
authors: S
authors: Loder
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Shuli
authors: S
authors: Li
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Kay
authors: K
authors: Shigemori
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Jonathan
authors: J
authors: Peterson
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: David
authors: D
authors: Cholok
authors: Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
authors: Jonathan A
authors: JA
authors: Forsberg
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Yuji
authors: Y
authors: Mishina
authors: Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, MD, 20910, United States of America.
authors: Thomas A
authors: TA
authors: Davis
authors: Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI, 48109, United States of America.
authors: Benjamin
authors: B
authors: Levi
mesh_terms: D000328:Adult; D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002056:Burns / Q000150:complications*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009132:Muscles / Q000166:cytology*; D009999:Ossification, Heterotopic / Q000209:etiology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051898:Smad1 Protein; D051902:Smad5 Protein; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D015675:Osteocalcin