Changes in macrophage and inflammatory cytokine expressions during fracture healing in an ovariectomized mice model

BackgroundMacrophages and inflammatory cytokines play important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture healing under the condition of postmenopausal osteoporosis have not been fully revealed.MethodsTibia transverse fracture was established 12weeks after ovariectomy or sham operation in 16-week old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28days after fracture for radiological and histological examinations. M1/M2 inflammatory macrophages, osteal macrophages and gene expressions of tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta and macrophage conversion related molecules in the fracture haematoma or callus were also detected.ResultsThe processes of fracture healing, especially the phases of endochondral ossification and callus remodeling, were delayed in ovariectomized mice. The expressions of tumor necrosis factor-alpha and interleukin-6, but not interleukin-1 beta, in the fracture haematoma or callus were disturbed. Expressions of tumor necrosis factor-alpha were decreased at 1, 14 and 21days post-fracture (DPF), and were increased at 3, 5 and 7 DPF. Interleukin-6 expressions at 1, 3 and 21 DPF were significantly increased. We found the decreases in M1 and M2 macrophages at 1 DPF of the initial inflammatory stage. M2 macrophages at 14 DPF of the middle stage and osteal macrophages at 14, 21 and 28 DPF of the middle and late stages of fracture healing were also reduced in ovariectomized mice.ConclusionsThe expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.

Automated summary

Macrophages and inflammatory cytokines play crucial roles in bone fracture healing. However, their expression patterns are disrupted in ovariectomized mice with postmenopausal osteoporosis, potentially contributing to impaired fracture healing.