Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing
Autor: | Shawn Loder, Amanda K. Huber, John Li, Yuji Mishina, Dylan Nycz, Yashar S. Niknafs, S L Kunkel, William F. Carson, Michael Sorkin, Rajasree Menon, Kaetlin Vasquez, Aaron W. James, Laurie K. McCauley, Shuli Li, Chase A. Pagani, Noelle D. Visser, Melissa Scola, Shailesh Agarwal, Charles Hwang, Nicole Patel, Katherine A. Gallagher, Jiajia Xu, Benjamin Levi |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Cellular differentiation General Physics and Astronomy Monocytes 0302 clinical medicine Macrophage lcsh:Science Multidisciplinary Cell Differentiation medicine.anatomical_structure 030220 oncology & carcinogenesis Cytokines medicine.symptom Burns Science Systems analysis CD47 Antigen Mice Transgenic General Biochemistry Genetics and Molecular Biology Article Transforming Growth Factor beta1 03 medical and health sciences Phagocytosis medicine Animals Progenitor cell Inflammation Wound Healing Ossification business.industry Monocyte Macrophages Ossification Heterotopic Mesenchymal stem cell Mesenchymal Stem Cells General Chemistry medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Gene Expression Regulation Osteoimmunology Cancer research lcsh:Q Heterotopic ossification Transforming growth factor beta Wound healing business Peptides |
Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) |
ISSN: | 2041-1723 |
Popis: | Heterotopic ossification (HO) is an aberrant regenerative process with ectopic bone induction in response to musculoskeletal trauma, in which mesenchymal stem cells (MSC) differentiate into osteochondrogenic cells instead of myocytes or tenocytes. Despite frequent cases of hospitalized musculoskeletal trauma, the inflammatory responses and cell population dynamics that regulate subsequent wound healing and tissue regeneration are still unclear. Here we examine, using a mouse model of trauma-induced HO, the local microenvironment of the initial post-injury inflammatory response. Single cell transcriptome analyses identify distinct monocyte/macrophage populations at the injury site, with their dynamic changes over time elucidated using trajectory analyses. Mechanistically, transforming growth factor beta-1 (TGFβ1)-producing monocytes/macrophages are associated with HO and aberrant chondrogenic progenitor cell differentiation, while CD47-activating peptides that reduce systemic macrophage TGFβ levels and help ameliorate HO. Our data thus implicate CD47 activation as a therapeutic approach for modulating monocyte/macrophage phenotypes, MSC differentiation and HO formation during wound healing. Aberrant tissue repair may result in heterotopic ossification (HO), but how this process is regulated by local inflammatory responses is still unclear. Here the authors show, using a mouse burn/trauma model, that TGFβ-producing monocytes/macrophages at the injury site contribute to HO induction, while CD47 activation helps antagonize this process. |
Databáze: | OpenAIRE |
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