Zhou Lei, Wang Jianqiang, Mu Weidong
Department of Orthopaedics, Shandong Provincial Hospital, Shandong University Jinan, Shandong, China.
Department of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University Xuzhou, Jiangsu, China.
Am J Transl Res. 2023 Dec 15;15(12):6751-6759. eCollection 2023.
To investigate the role of bone morphogenetic protein-2 (BMP-2) in promoting fracture healing in animal models.
Mouse models with muscle bag heterotopic osteogenesis (HO) were divided into a HO control group (not implanted with 250 μg rhBMP-2 bone repairing material), and a HO observation group (implanted with 250 μg rhBMP-2 bone repairing material); while rat models with bone defect (BD) were divided into a BD control group (not implanted with 250 μg rhBMP-2 bone repairing material) and a BD observation group (implanted with 250 μg rhBMP-2 bone repairing material). At 4 weeks after HO establishment, the new bone formation at the operation site was observed through visual inspections and X-ray scanning. The content of serum alkaline phosphatase (ALP) was detected by automatic biochemical analyzer. The formation of new bone at the operative sites was observed by Hematoxylin and eosin staining and Masson staining. At 0, 2, 4 and 8 weeks after operation, the growth of the defect area and its surrounding callus were observed by X-ray scanning. At 4 and 8 weeks after bone defect establishment in the mouse models, the histological changes and osteogenesis of the bone defect site were observed.
The heterotopic osteogenesis experiment showed that at 4 weeks after operation, the mass at the muscle bag in the HO observation group became larger in contrast to the HO control group. X-ray scanning showed that there was obvious irregular bone shadow at the back muscle bag of mice from the HO observation group. The content of serum ALP in the HO observation group was significantly higher than that in the HO control group (all <0.05). The muscle pocket in the HO observation group showed higher ectopic osteogenic activity comparing with the HO control group. Histological staining showed that bone tissue structure was visible in the newly regenerated bone, forming bone trabeculae and bone marrow tissue. Under the microscope, a large number of osteoblasts arranged neatly in a cubic shape presented at the edge of the new bone, and there were bone lacunae formed, and the bone tissue was in a relatively mature stage. In the rat bone defect models, X-ray scanning showed that the high-density development area was further increased. There was a large amount of callus formation in the bone defect area of the BD observation group, while the BD control group still had no high-density development. At 8 weeks after operation, the high-density development area decreased, indicating that there was partial absorption of callus, while there was still no high-density development in the BD control group. The callus of the bone defect area in the BD observation group was reduced and the defect area was gradually repaired, while the bone defect in the BD control group was still obvious and the bone repair was not completed.
BMP-2 could promote osteoblast differentiation and bone defect osteogenesis . Thus, it is worthy of clinical application.
探讨骨形态发生蛋白-2（BMP-2）在动物模型中促进骨折愈合的作用。
将肌肉袋异位成骨（HO）小鼠模型分为HO对照组（未植入250μg重组人骨形态发生蛋白-2骨修复材料）和HO观察组（植入250μg重组人骨形态发生蛋白-2骨修复材料）；将骨缺损（BD）大鼠模型分为BD对照组（未植入250μg重组人骨形态发生蛋白-2骨修复材料）和BD观察组（植入250μg重组人骨形态发生蛋白-2骨修复材料）。HO模型建立后4周，通过肉眼观察和X线扫描观察手术部位新骨形成情况。用自动生化分析仪检测血清碱性磷酸酶（ALP）含量。通过苏木精-伊红染色和Masson染色观察手术部位新骨形成情况。术后0、2、4和8周，通过X线扫描观察缺损区及其周围骨痂生长情况。在小鼠模型骨缺损建立后4周和8周，观察骨缺损部位的组织学变化和成骨情况。
异位成骨实验显示，术后4周，HO观察组肌肉袋处肿物较HO对照组增大。X线扫描显示，HO观察组小鼠背部肌肉袋处有明显不规则骨影。HO观察组血清ALP含量显著高于HO对照组（均P<0.05）。HO观察组肌肉袋异位成骨活性高于HO对照组。组织学染色显示，新生骨中有可见的骨组织结构，形成骨小梁和骨髓组织。显微镜下，新骨边缘有大量呈立方形整齐排列的成骨细胞，有骨陷窝形成，骨组织处于相对成熟阶段。在大鼠骨缺损模型中，X线扫描显示高密度显影区进一步增大。BD观察组骨缺损区有大量骨痂形成，而BD对照组仍无高密度显影。术后8周，高密度显影区减小，提示骨痂有部分吸收，而BD对照组仍无高密度显影。BD观察组骨缺损区骨痂减少，缺损区逐渐修复，而BD对照组骨缺损仍明显，骨修复未完成。
BMP-2可促进成骨细胞分化和骨缺损成骨，值得临床应用。
