School of Podiatric Medicine - Student Research

Document Type

Poster

Publication Date

2026

Abstract

Background: High-risk patients, such as those with diabetic neuropathy, often experience prolonged and dysregulated inflammation during bone healing. The 5-lipoxygenase (5LO) pathway is a key mediator of inflammation and bone resorption and may influence these outcomes. Therefore, understanding the skeletal features associated with 5LO genetic deletion may help identify therapeutic opportunities to improve healing in high-risk patients.

Objective: To determine how genetic deletion of 5LO affects skeletal structure and macrophage phenotypes, with the goal of identifying therapeutic targets to improve bone healing in high-risk patients.

Materials and Methods: A total of 10, adult (3 months old), 129/SvEv male mice were utilized in this study, being 5 wild type (WT) and 5 genetically modified for 5LO (homozygous knockout, 5LOKO) (IACUC #95892701017). Skeletal morphology and macrophages phenotypes were compared between both strains. Femurs were collected for histologic evaluation, including osteocyte lacunar assessment and immunohistochemistry of bone marrow M1 (CD80), M2 (CD163) and total macrophages (F4/80).

Results: 5LOKO mice showed significantly reduced osteocyte connectivity, canalicular structure, and branching compared to WT, which may reflect increased cortical bone organization. Bone marrow analyses revealed distinct macrophage polarization profiles, with 5LOKO mice exhibiting a reduced total macrophage population (F4/80+ cells) and a significant decrease in the pro-inflammatory M1 subset (CD80+), while the anti-inflammatory M2 subset (CD163+) remained unchanged compared to WT controls.

Conclusion: Our findings highlight an important role for 5LO in bone homeostasis, including macrophages phenotype and osteocyte distribution. Together, this data suggests that targeting 5LO pathway or its receptors may support improved bone health.

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