伤口愈合
祖细胞
异位骨化
间充质干细胞
免疫学
人口
单核细胞
巨噬细胞
医学
癌症研究
细胞生物学
干细胞
生物
再生(生物学)
解剖
体外
环境卫生
生物化学
作者
Michael Sorkin,Amanda K. Huber,Charles Hwang,William F. Carson,Rajasree Menon,John Li,Kaetlin Vasquez,Chase A. Pagani,Nicole Patel,Shuli Li,Noelle D. Visser,Yashar S. Niknafs,Shawn Loder,Melissa Scola,Dylan Nycz,Katherine A. Gallagher,Laurie K. McCauley,Jiajia Xu,Aaron W. James,Shailesh Agarwal,S. L. Kunkel,Yuji Mishina,Benjamin Lévi
标识
DOI:10.1038/s41467-019-14172-4
摘要
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.
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