Magnesium-containing intramedullary nails promote fracture healing in type 2 diabetic animal model via recruiting regulatory T cells into the fracture callus.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42518653.
- Also identified by DOI 10.1016/j.bioactmat.2026.07.014 and PMC identifier 13383014.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Magnesium-containing intramedullary nails (Mg-IMN) have been shown to promote fracture healing across various types of fractures, including osteoporotic and atypical femoral fractures. However, their role in the challenging chronic inflammatory type 2 diabetes (T2D) fracture healing remains unclear. In this study, we investigated the effect of Mg-IMN on fracture healing in a T2D mouse model and explored the involvement of regulatory T cells (Tregs) in this process. Our results demonstrated that Mg-IMN promotes fracture healing in Lepr<sup>db/db</sup> T2D mice. At 5 days post-fracture, flow cytometry showed an increased number of Tregs in the fracture callus. Notably, depletion of Tregs via injection of PC61 neutralizing antibody abolished the promotive effect of Mg-IMN, indicating the critical role of Tregs in this process. Bulk RNA sequencing of the bone callus at 5 days post-fracture revealed significant enrichment of pathways related to chemokine signaling and CCR chemokine receptor interactions, suggesting a mechanism of Treg recruitment. Transwell migration assays <i>in vitro</i> preliminarily indicated the chemotactic effect of CCL19 and CCL21 in recruiting Tregs. Furthermore, Mg<sup>2+</sup> treatment enhanced the mRNA expression levels of amphiregulin (<i>Areg</i>) and granulin (<i>Grn</i>) in Tregs, as indicated by qRT-PCR analysis. These findings may pave the way for new applications of Mg-IMN in fracture repair and provide unique insights into osteoimmunology during the complex process of T2D fracture healing.