Kan Tianyou, He Zihao, Du Jingke, Xu Mingming, Cui Junqi, Han Xuequan, Tong Dake, Li Hanjun, Yan Mengning, Yu Zhifeng
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Arthritis Clinic & Research Center, Peking University People's Hospital, Beijing, China.
J Orthop Translat. 2022 Sep 24;37:37-45. doi: 10.1016/j.jot.2022.07.006. eCollection 2022 Nov.
Osteogenesis and angiogenesis are important for bone fracture healing. Irisin is a muscle-derived monokine that is associated with bone formation.
To demonstrate the effect of irisin on bone fracture healing, closed mid-diaphyseal femur fractures were produced in 8-week-old C57BL/6 mice. Irisin was administrated intraperitoneally every other day after surgery, fracture healing was assessed by using X-rays. Bone morphometry of the fracture callus were assessed by using micro-computed tomography. Femurs of mice from each group were assessed by the three-point bending testing. Effect of irisin on osteogenic differentiation in mesenchymal stem cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), alkaline phosphatase staining and alizarin red staining. Angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by qRT-PCR, migration tests, and tube formation assays.
Increased callus formation, mineralization and tougher fracture healing were observed in the irisin-treated group than in the control group, indicating the better fracture callus healing due to Irisin treatment. The vessel surface and vessel volume fraction of the callus also increased in the irisin-treated group. The expression of BMP2, CD31, and VEGF in callus were enhanced in the irisin-treated group. In mouse bone mesenchymal stem cells, irisin promoted ALP expression and mineralization, and increased the expression of osteogenic genes, including , , , , and . Irisin also promoted HUVEC migration and tube formation. Expression of angiogenic genes, including , , , , , and in HUVECs were increased by irisin.
All the results indicate irisin can promote fracture healing through osteogenesis and angiogenesis. These findings help in the understanding of muscle-bone interactions during fracture healing.
Irisin was one of the most important monokine secreted by skeletal muscle. Studies have found that irisin have anabolic effect one bone remodeling through affecting osteocyte and osteoblast. Based on our study, irisin could promote bone fracture healing by increasing bone mass and vascularization, which provide a potential usage of irisin to promote fracture healing and improve clinical outcomes.
成骨作用和血管生成对骨折愈合很重要。鸢尾素是一种与骨形成相关的肌肉衍生单因子。
为了证明鸢尾素对骨折愈合的影响，在8周龄的C57BL/6小鼠中制造了闭合性股骨干中段骨折。术后每隔一天腹腔注射鸢尾素，通过X射线评估骨折愈合情况。使用微型计算机断层扫描评估骨折痂的骨形态计量学。通过三点弯曲试验评估每组小鼠的股骨。通过定量实时聚合酶链反应（qRT-PCR）、碱性磷酸酶染色和茜素红染色评估鸢尾素对间充质干细胞成骨分化的影响。通过qRT-PCR、迁移试验和管形成试验评估人脐静脉内皮细胞（HUVECs）的血管生成。
与对照组相比，鸢尾素治疗组观察到骨痂形成增加、矿化增加且骨折愈合更坚固，表明鸢尾素治疗可使骨折痂愈合更好。鸢尾素治疗组骨痂的血管表面积和血管体积分数也增加。鸢尾素治疗组骨痂中BMP2、CD31和VEGF的表达增强。在小鼠骨髓间充质干细胞中，鸢尾素促进碱性磷酸酶表达和矿化，并增加成骨基因的表达，包括、、、、和。鸢尾素还促进HUVEC迁移和管形成。鸢尾素增加了HUVEC中包括、、、、和在内的血管生成基因的表达。
所有结果表明鸢尾素可通过成骨作用和血管生成促进骨折愈合。这些发现有助于理解骨折愈合过程中的肌肉-骨相互作用。
鸢尾素是骨骼肌分泌的最重要的单因子之一。研究发现鸢尾素通过影响骨细胞和成骨细胞对骨重塑具有合成代谢作用。基于我们的研究，鸢尾素可通过增加骨量和血管化促进骨折愈合，这为鸢尾素促进骨折愈合和改善临床结果提供了潜在用途。
