Reg Gene Expression in Periosteum after Fracture and Its In Vitro Induction Triggered by IL-6

The periosteum is a thin membrane that surrounds the outer surface of bones and participates in fracture healing. However, the molecular signals that trigger/initiate the periosteal reaction are not well established. We fractured the rat femoral bone at the diaphysis and fixed it with an intramedullary inserted wire, and the expression of regenerating gene ( ) , which encodes a tissue regeneration/growth factor, was analyzed. Neither bone/marrow nor muscle showed gene expression before or after the fracture. By contrast, the periosteum showed an elevated expression after the fracture, thereby confirming the localization of expression exclusively in the periosteum around the fractured areas. Expression of the family increased after the fracture, followed by a decrease to basal levels by six weeks, when the fracture had almost healed. In vitro cultures of periosteal cells showed no expression, but the addition of IL-6 significantly induced gene expression. The addition of IL-6 also increased the cell number and reduced pro-apoptotic gene expression of . The increased cell proliferation and reduction in gene expression were abolished by transfection with siRNA, indicating that these IL-6-dependent effects require the gene expression. These results indicate the involvement of the IL-6/Reg pathway in the osteogenic response of the periosteum, which leads to fracture repair.