Identification of circulating murine CD34+OCN+ cells |
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Authors: | RYAN R KELLY LINDSAY T MCDONALD VINCENT D PELLEGRINI JAMES J CRAY AMANDA C LARUE |
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Institution: | 1. Research Services, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA;2. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA;3. Department of Orthopedics, Medical University of South Carolina, Charleston, SC, USA;4. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA;5. Division of Anatomy, The Ohio State University, Columbus, OH, USA |
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Abstract: | Background aimsPrevious studies identified a circulating human osteoblastic population that expressed osteocalcin (OCN), increased following fracture and pubertal growth, and formed mineralized colonies in vitro and bone in vivo. A subpopulation expressed CD34, a hematopoietic/endothelial marker. These findings led to our hypothesis that hematopoietic-derived CD34+OCN+ cells exist in the circulation of mice and are modulated after fracture.MethodsFlow cytometry was used to identify CD34+OCN+ cells in male B6.SJL-PtprcaPepcb/BoyJ and Vav-Cre/mTmG (VavR) mice. Non-stabilized tibial fractures were created by three-point bend. Fractures were longitudinally imaged by micro-computed tomography, and immunofluorescent staining was used to evaluate CD34+OCN+ cells within fracture callus. AMD3100 (10 mg/kg) was injected subcutaneously for 3 days and the CD34+OCN+ population was evaluated by flow cytometry.ResultsCirculating CD34+OCN+ cells were identified in mice and confirmed to be of hematopoietic origin (CD45+; Vav1+) using two mouse models. Both circulating and bone marrow-derived CD34+OCN+ cells peaked three weeks post-non-stabilized tibial fracture, suggesting association with cartilage callus transition to bone and early mineralization. Co-expression of CD34 and OCN in the fracture callus at two weeks post-fracture was observed. By three weeks, there was 2.1-fold increase in number of CD34+OCN+ cells, and these were observed throughout the fracture callus. AMD3100 altered CD34+OCN+ cell levels in peripheral blood and bone marrow.DiscussionTogether, these data demonstrate a murine CD34+OCN+ circulating population that may be directly involved in fracture repair. Future studies will molecularly characterize CD34+OCN+ cells, determine mechanisms regulating their contribution, and examine if their number correlates with improved fracture healing outcomes. |
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Keywords: | circulating osteoprogenitor fracture hematopoietic stem cell mesenchymal stromal cell mobilization |
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