Immune cells in the bone healing process

ABSTRACT: Bone is a unique organ able to regenerate after severe traumatic injuries. However, regeneration is governed by the interplay between systems located in the site of injury. The immune system initiates the inflammatory response in the early phase of healing. Therefore, the global role of T-cells and B-cells in the bone regeneration and the resulting bone quality is the focus of this study. A standard unilateral closed fracture was created in the femora to study the overlapping phases of bone healing. Besides wild type (WT) a model of recombination activating gene 1 knockout (RAG1-/-) mice that lacking mature T and B-cells were investigated. In addition, at D7 the individual role of T-cells and B-cells were investigated through the (TCRβδ) and JHT-/- knockouts respectively. Radiological, biomechanical, histological and imaging were utilized along with differential expression analysis. RAG1-/- mice showed higher biomechanical stiffness in intact bone when compared to the WT mice. Higher mineralization at early stage was seen in the RAG1-/- and bone devoid of T-cells (TCRβδ-/-) including. However, healing in bone devoid of B-cells (JHT-/-) was not apparently deviant of that of WT. Interestingly, second harmonic photon microscopy revealed an disorganized collagen fibers in the RAG1-/- contemporary with the expression analysis showing dysregulation in the expression of ColI subunits. Gene network analysis reflected the expected down regulation of T cell related genes in the RAG1-/- but not the B-cell related genes. This can hint to backup mechanism compensating the lack of mature B-cells. Furthermore, differentially expressed genes in RAG1-/- mice showed an impact on angiogenesis, cytokines & growth factors and bone remodeling, and BMP signaling array throughout the healing process. This asserts the focus on the adaptive immune system in two directions: 1) suggested role of T-cells in governing bone quality. 2) indicated importance of B-cells for bone regeneration through backup mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE99128 | GEO | 2020/05/04

REPOSITORIES: GEO