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

Department of Orthopedic Surgery, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara, Nara 630-8305, Japan
Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan
Department of Diagnostic Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
Department of Laboratory Medicine and Pathology, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka 591-8025, Japan
Department of Orthopedic Surgery, Ookuma Hospital, 2-17-13 Kuise-honmachi, Amagasaki, Hyogo 660-0814, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(11), 2257;
Received: 12 September 2017 / Revised: 24 October 2017 / Accepted: 24 October 2017 / Published: 27 October 2017
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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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 (Reg) I, which encodes a tissue regeneration/growth factor, was analyzed. Neither bone/marrow nor muscle showed Reg I gene expression before or after the fracture. By contrast, the periosteum showed an elevated expression after the fracture, thereby confirming the localization of Reg I expression exclusively in the periosteum around the fractured areas. Expression of the Reg 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 Reg I expression, but the addition of IL-6 significantly induced Reg I gene expression. The addition of IL-6 also increased the cell number and reduced pro-apoptotic gene expression of Bim. The increased cell proliferation and reduction in Bim gene expression were abolished by transfection with Reg I siRNA, indicating that these IL-6-dependent effects require the Reg I 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. View Full-Text
Keywords: bone regeneration; fracture; Reg (regenerating gene); IL-6; periosteum; Bim bone regeneration; fracture; Reg (regenerating gene); IL-6; periosteum; Bim

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Tohma, Y.; Dohi, Y.; Shobatake, R.; Uchiyama, T.; Takeda, M.; Takasawa, S.; Tanaka, Y.; Ohgushi, H. Reg Gene Expression in Periosteum after Fracture and Its In Vitro Induction Triggered by IL-6. Int. J. Mol. Sci. 2017, 18, 2257.

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