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.
Int J Mol Sci. 2017 Oct 27;18(11):2257. doi: 10.3390/ijms18112257.
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.
骨膜是一层薄的膜，环绕在骨的外表面，并参与骨折愈合。然而，触发/启动骨膜反应的分子信号尚未得到很好的确立。我们在大鼠股骨骨干处骨折，并使用髓内插入的金属丝固定，分析了再生基因()的表达，该基因编码一种组织再生/生长因子。在骨折前后，骨/骨髓和肌肉均未显示基因表达。相比之下，骨折后骨膜的表达升高，从而证实了的表达仅局限于骨折区域周围的骨膜。骨折后家族的表达增加，然后在六周时降至基础水平，此时骨折几乎愈合。体外培养的骨膜细胞没有表达，但添加白细胞介素 6(IL-6)可显著诱导基因表达。添加白细胞介素 6 还增加了的细胞数量，并减少了促凋亡基因的表达。用 siRNA 转染可消除细胞增殖的增加和基因表达的减少，表明这些白细胞介素 6 依赖性效应需要基因表达。这些结果表明 IL-6/Reg 途径参与了骨膜的成骨反应，从而导致骨折修复。
