Objective: To investigate the role of bone morphogenetic protein-2 (BMP-2) in promoting fracture healing in animal models.
Methods: 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.
Results: 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 P<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.
Conclusions: BMP-2 could promote osteoblast differentiation and bone defect osteogenesis in vivo. Thus, it is worthy of clinical application.
Keywords: Bone morphogenetic proteins-2; bone defect; heterotopic osteogenesis; mice.
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