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
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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