Decisive differences in the bone repair processes of the metaphysis and diaphysis in young mice

Abstract

Fractures are common traumatic injuries that mainly occur in the metaphyses of long bones such as the proximal humerus, distal radius, and proximal femur. However, most studies of fracture repair processes have focused on the diaphyseal region. In this study, we compared the bone repair processes of the metaphysis and the diaphysis of the mouse tibia. Bone apertures were formed in the tibial metaphysis and diaphysis. At indicated times after surgery, samples were collected, and the healing process was investigated using micro-computed tomography, as well as histological, immunohistochemical, and mRNA expression analyses. In the metaphysis, cartilage formation was not detected on the periosteal side. The bone aperture was filled with newly formed bone produced from bone marrow at day 7. In the case of the diaphysis, cartilage was formed around the aperture at day 4 and sequentially replaced by bone on the periosteal side. The bone aperture was filled with newly formed bone at day 14. In the bone marrow, expression of the osteogenic markers such as alkaline phosphatase, osteocalcin, and type I collagen, appeared earlier with metaphyseal injury than with diaphyseal injury. The mRNA expression of chondrogenesis markers was markedly upregulated in the diaphysis compared with that in the metaphysis on the periosteal side. These results indicate differences in the bone repair processes of the two regions, suggesting functional heterogeneity of the periosteum and bone marrow mesenchymal cells in response to bone fractures.