Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing

被引：137

作者：

Sorkin, Michael ^{[1
]}

Huber, Amanda K. ^{[1
]}

Hwang, Charles ^{[1
]}

Carson, William F. ^{[2
]}

Menon, Rajasree ^{[3
]}

Li, John ^{[1
]}

Vasquez, Kaetlin ^{[1
]}

Pagani, Chase ^{[1
]}

Patel, Nicole ^{[1
]}

Li, Shuli ^{[1
]}

Visser, Noelle D. ^{[1
]}

Niknafs, Yashar ^{[1
]}

Loder, Shawn ^{[1
]}

Scola, Melissa ^{[2
]}

Nycz, Dylan ^{[4
]}

Gallagher, Katherine ^{[4
]}

McCauley, Laurie K. ^{[5
]}

Xu, Jiajia ^{[6
]}

James, Aaron W. ^{[6
]}

Agarwal, Shailesh ^{[1
]}

Kunkel, Stephen ^{[2
]}

Mishina, Yuji ^{[7
]}

Levi, Benjamin ^{[1
]}

机构：

[1] Univ Michigan, Dept Surg, Sect Plast Surg, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Surg, Div Vasc Surg, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA

[6] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA

[7] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

MACROPHAGE PLASTICITY; OF-LIFE; CELLS; BETA; POLARIZATION; DEPLETION; RECEPTOR; INJURY;

D O I：

10.1038/s41467-019-14172-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 (TGF beta 1)-producing monocytes/macrophages are associated with HO and aberrant chondrogenic progenitor cell differentiation, while CD47-activating peptides that reduce systemic macrophage TGF beta 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.

引用

页数：17

共 44 条

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