T Lymphocytes Influence the Mineralization Process of Bone

Abstract

Bone is a unique organ able to regenerate itself after injuries. This regeneration requires the local interplay between different biological systems such as inflammation and matrix formation. Structural reconstitution is initiated by an inflammatory response orchestrated by the host immune system. However, the individual role of T cells and B cells in regeneration and their relationship to bone tissue reconstitution remain unknown. Comparing bone and fracture healing in animals with and without mature T and B cells revealed the essential role of these immune cells in determining the tissue mineralization and thus the bone quality. Bone without mature T and B cells is stiffer when compared to wild-type bone thus lacking the elasticity that helps to absorb forces, thus preventing fractures. In-depth analysis showed dysregulations in collagen deposition and osteoblast distribution upon lack of mature T and B cells. These changes in matrix deposition have been correlated with T cells rather than B cells within this study. This work presents, for the first time, a direct link between immune cells and matrix formation during bone healing after fracture. It illustrates specifically the role of T cells in the collagen organization process and the lack thereof in the absence of T cells.

Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone

“…This both corresponds and differs from earlier studies; unaltered bone formation has been observed before in CD8-depleted mice and transgenic mice lacking T and B cells. 4,6 However, the transgenic mice had stiffer bones, in contrast to our results, but can be explained by the differences that the study was conducted in mice, with shaft fractures, and lacked both T and B cells. 4 On the other hand, they noticed a difference in collagen deposition in the fracture callus; the collagen fibrils were more disorganized in the fracture callus in transgenic mice compared to wildtype mice.…”

“…That is, after we depleted the CD8 + cells, the pull‐out force decreased, although the bone formation in the drill holes was the same as in the controls. This both corresponds and differs from earlier studies; unaltered bone formation has been observed before in CD8‐depleted mice and transgenic mice lacking T and B cells . However, the transgenic mice had stiffer bones, in contrast to our results, but can be explained by the differences that the study was conducted in mice, with shaft fractures, and lacked both T and B cells .…”

“…Once inside, the immune cells can recruit other cells via chemotaxis, which can regenerate the tissue . A lack of T and B cells in mice prevents osteogenic progenitor cells to enter the fracture callus leading to a disorganized collagen deposition and stiffer, more brittle bone . On the other hand, clinical and experimental studies have revealed a correlation between delayed fracture healing and elevated levels of circulating cytotoxic (CD8 + ) T cells .…”

“…[1][2][3] A lack of T and B cells in mice prevents osteogenic progenitor cells to enter the fracture callus leading to a disorganized collagen deposition and stiffer, more brittle bone. 4 On the other hand, clinical and experimental studies have revealed a correlation between delayed fracture healing and elevated levels of circulating cytotoxic (CD8 þ ) T cells. 5,6 Patients with delayed fracture healing show higher levels of a CD8 þ subpopulation (T EMRA cells), in peripheral blood.…”

Research in Fracture Healing and Its Clinical Applications in the Veterinary Practice

“…No cartilage remains; 28 days: remodeling phase. Histological samples stained with Movat Pentachrome: bone = yellow; bone marrow =purple; cartilage = blue-green, muscle = orange; connective tissue = light blue [2,4,6,15,[34][35][36][37][38][39][40][41][42][43]. Periost has been carefully elevated from the bone and was stained with hematoxylin eosin.…”