M2 macrophages are closely associated with accelerated clavicle fracture healing in patients with traumatic brain injury: a retrospective cohort study

Abstract

BackgroundMounting evidence indicate patients with traumatic brain injury (TBI) have an accelerated fracture healing. The healing process of bone fractures is greatly dependent on infiltrated macrophages. The macrophages are categorized into M1 or M2 phenotypes with different functions. This study is aimed to address the potential role of subtypes of macrophages in the process of fracture healing in patients with TBI.MethodsTwenty-five cases of clavicle fracture alone (CF group) and 22 cases of clavicle fracture concomitant with TBI (CFT group) were retrospectively analyzed in this study. Callus tissues were harvested during operations. The expressions of COX-2, CD206, and CD68 were measured with immunohistochemistry.ResultsThe percentages of M2 macrophages in total macrophages increased after bone fracture in both groups, while the percentages of M1-type macrophages are decreased. Interestingly, the increased percentages of M2 macrophages are significantly higher in CFT group than in CF group. Compared to CF group, the fracture callus volume was much larger (21.9 vs 8.5 cm3) and the fracture healing time was much shorter (82.2 vs 127.0 days) in CFT group. The percentage of M2 macrophages was negatively correlated with fracture healing time in patients (r = − 0.575, p < 0.01).ConclusionsThe findings suggest that the percentages of M2 macrophages in callus tissues increased dramatically during the repairing stage in both CF and CFT group. Percentages of M2 macrophages are associated with accelerated fracture healing in patients with TBI. M2 macrophage polarization during the stage of bone regeneration may play a vital role in promoting bone fracture healing.

Osteoimmunology drives dental implant osseointegration: A new paradigm for implant dentistry

“…During fracture healing, M2 macrophages participate in both the resolution phase of inflammation and in the homing of mesenchymal stem cells (MSCs) [ 32 , 33 ]. Also, M2 contributes to the ossification phase of fracture repair [ 34 , 35 ]. Surprisingly, for epimorphic regeneration of axolotl limb and zebrafish tail fin regeneration, macrophages also gradually shift to an M2 phenotype during the tissue remodeling stage [ 6 , 36 ].…”

Modeling the Macrophage-Mediated Inflammation Involved in the Bone Fracture Healing Process

“…The proposed new model (1)-(10) is used to study the importance of macrophages during the inflammatory and repair phases of the bone fracture healing process, which occur within the first 21 days after trauma [11,13]. It is also used to investigate the evolution of a broken bone under normal and pathological conditions.…”

“…Furthermore, during inflammation, classically activated macrophages attract mesenchymal lineage cells (MSCs) to the injury site and activate the healing process [3,10,12]. In contrast, during the repair phase, alternatively activated macrophages promote MSC proliferation and differentiation, and accelerate bone healing [10,13]. However, the exact mechanisms by which macrophages contribute to bone healing remain unclear [3,10,14].…”

“…However, the exact mechanisms by which macrophages contribute to bone healing remain unclear [3,10,14]. Also, the interaction between macrophages and tissue cells, as well as the importance of classically and alternatively activated macrophages during the bone healing process, are still not clearly understood [10,12,13].…”

Inflammation in Cancellous and Cortical Bone Healing

“…Most studies on macrophages in fracture healing have focused on shaft models and mainly used markers that may be classified as "canonical" macrophage markers, such as the CD11b/CD18-complex (Mac-1), CD68, F4/80 and CD14, which largely lack discriminatory power on polarization. M2 have been reported to be increased in clavicle fractures of patients with traumatic brain injury, a clinically known state of increased fracture healing potential (R. Zhang et al 2018). This indicates M2 macrophages to be of particular importance to bone healing.…”