Study Of ERK5 In The Healing Process Of Osteoporotic Fracture In Mice

Objective: Osteoporosis will cause bone loss,damage in the structure of bone,and easily lead to the occurrence of fracture due to the disorder of bone formation and absorption,ERK5 can promote the proliferation and differentiation of osteoblasts,regulate the expression of osteogenesis-related proteins,but its mechanism of bone formation and fracture healing in vivo is not clear.Therefore,by studying the role of ERK5 in the process of osteoporotic fracture healing,it will provide a new method for clinical exploration of prevention and treatments to osteoporosis and osteoporotic fractures.Methods: Six-week-old Kunming mice were randomly divided into four groups.The osteoporotic animal model was established by surgical removal of the bilateral ovaries.Then the osteoporotic fracture model was established by making the right femur be cut off and then be repositioned and fixed with acupunctures.After the model was successfully made,the experimental group was injected with ERK5-specific blocker XMD8-92 intraperitoneally,and a certain number of mice were sacrificed at 1 week,2 weeks and 4 weeks respectively,X-ray examination,Micro-CT scan and three-dimensional reconstruction,HE staining and immunohistochemically staining of bone callus were performed to observe the growth of trabecular bone,and expression of osteoblast-related protein and ERK5.The role of ERK5 making in the healing process of osteoporotic fractures was then analyzed.Results: The mice in the experimental group were injected with XMD8-92 at the 2nd week and the 4th week.In the fracture group,the callus of the mice grew faster,there were more and thicker trabecular bone,the expression of the osteoblast-associated protein ALP,Runx-2 was higher(P <0.05).The callus grew more slowly with less and thinner trabecular bone,and the expression of the osteoblast-associated protein ALP,Runx-2 was lower in the fracture + XMD8-92 group(P <0.05).Compared with osteoporotic fracture group,the osteoporotic fracture + XMD8-92 group showed less and more disorderly in trabecular bone formation,the growth of callus was significantly delayed,and the expression of ALP,Runx-2 was significantly lower(P <0.05).Conclusion: ERK5 plays an important role in promoting osteoblast proliferation and differentiation.When it is blocked by specific blocker XMD8-92 in vivo,activation is restricted,the downstream signaling pathway is blocked,and the expression and synthesis of osteoblast-associated protein during fracture healing process is blocked,the rate and quality of callus formation decreased,the number of trabecular bone decreased and showed structural disorder.The early healing process of femoral fractures in mice was hindered,and the factors can be associated with the osteoclasts role of osteoporosis and further impact in the process of osteoporotic fracture healing.Therefore,ERK5 plays an important physiological role in the process of osteoporotic fracture healing,which can provide a new research direction and target for the clinical treatment on osteoporosis and osteoporotic fractures.