» Articles » PMID: 38455063

Temporal Dynamics of Immune-stromal Cell Interactions in Fracture Healing

Overview
Journal Front Immunol
Date 2024 Mar 8
PMID 38455063
Authors
Affiliations
Soon will be listed here.
Abstract

Bone fracture repair is a complex, multi-step process that involves communication between immune and stromal cells to coordinate the repair and regeneration of damaged tissue. In the US, 10% of all bone fractures do not heal properly without intervention, resulting in non-union. Complications from non-union fractures are physically and financially debilitating. We now appreciate the important role that immune cells play in tissue repair, and the necessity of the inflammatory response in initiating healing after skeletal trauma. The temporal dynamics of immune and stromal cell populations have been well characterized across the stages of fracture healing. Recent studies have begun to untangle the intricate mechanisms driving the immune response during normal or atypical, delayed healing. Various models of fracture healing, including genetic knockouts, as well as models of the fracture callus, have been implemented to enable experimental manipulation of the heterogeneous cellular environment. The goals of this review are to (1): summarize our current understanding of immune cell involvement in fracture healing (2); describe state-of-the art approaches to study inflammatory cells in fracture healing, including computational and models; and (3) identify gaps in our knowledge concerning immune-stromal crosstalk during bone healing.

Citing Articles

No bones about it: regulatory T cells promote fracture healing.

Griffith J, Luster A J Clin Invest. 2025; 135(2.

PMID: 39817452 PMC: 11735088. DOI: 10.1172/JCI188368.


CCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice.

Kannan R, Koh A, Kent 3rd R, Bhutada K, Wasi F, Wagner L J Cell Mol Med. 2024; 28(24):e70300.

PMID: 39721002 PMC: 11669326. DOI: 10.1111/jcmm.70300.

References
1.
Kasama T, Strieter R, Standiford T, Burdick M, Kunkel S . Expression and regulation of human neutrophil-derived macrophage inflammatory protein 1 alpha. J Exp Med. 1993; 178(1):63-72. PMC: 2191098. DOI: 10.1084/jem.178.1.63. View

2.
Tang G, Charo D, Wang R, Charo I, Messina L . CCR2-/- knockout mice revascularize normally in response to severe hindlimb ischemia. J Vasc Surg. 2004; 40(4):786-95. DOI: 10.1016/j.jvs.2004.07.012. View

3.
Kovtun A, Bergdolt S, Wiegner R, Radermacher P, Huber-Lang M, Ignatius A . The crucial role of neutrophil granulocytes in bone fracture healing. Eur Cell Mater. 2016; 32:152-62. DOI: 10.22203/ecm.v032a10. View

4.
Debnath S, Yallowitz A, McCormick J, Lalani S, Zhang T, Xu R . Discovery of a periosteal stem cell mediating intramembranous bone formation. Nature. 2018; 562(7725):133-139. PMC: 6193396. DOI: 10.1038/s41586-018-0554-8. View

5.
Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux N . B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006; 169(3):987-98. PMC: 1698808. DOI: 10.2353/ajpath.2006.060180. View