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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (6): 1171-1177. doi: 10.19723/j.issn.1671-167X.2021.06.027

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Early constant observation of the effect of deferoxamine mesylate on improvement of vascularized bone regeneration in SD rat skull critical size defect model

DU Wen-yu,YANG Jing-wen(),JIANG Ting()   

  1. Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
  • Received:2019-12-12 Online:2021-12-18 Published:2021-12-13
  • Contact: Jing-wen YANG,Ting JIANG E-mail:jingwen.yang@foxmail.com;jt_ketizu@163.com
  • Supported by:
    National Natural Science Foundation of China(81771045);Research Foundation of Peking University School and Hospital of Stomatology(PKUSS20180106)

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Abstract:

Objective: To investigate the effect of local administration of deferoxamine mesylate (DFO) on vascularization and osteogenesis and its ability to maintain the activity of hypoxia inducible factor-1α (HIF-1α), by constantly observing early changes of vessel-like structures and bone tissues during bone defects healing. Methods: Skull critical bone defect models were constructed on a total of thirty male SD rats (6-8 weeks old). The rats were randomly divided into experimental group (DFO group) or control group (normal saline group). 300 μL 200 μmol/L DFO solution or normal saline was locally injected on the 4th day after the defect was made. On the 5th, 7th, 10th, 14th, and 28th days after surgery, three rats in each group were sacrificed respectively. HE staining and Masson staining were performed to observe new bone formation and mineralization. HIF-1α immunohistochemistry staining was performed to examine relative expression of protein. Qualitative analysis and comparation were performed by t-tests on relative expression of HIF-1α, numbers of blood vessels and percentages of mineralization tissues of new bone areas. Results: On the 5th, 7th, 10th, 14th and 28th days after surgery, the average numbers of blood vessels were 30.40±12.15, 62.00±17.87, 73.43±15.63, 40.00±7.84, 48.71±11.64 in the DFO group, and 18.75±6.63, 19.13±2.80, 51.35±16.21, 27.18±7.32, 30.88±13.43 in the control group. The number of blood vessels in the DFO group was significantly higher than that of the control group at each time point (P<0.05). The mass of new bone in the DFO group was higher than that in the control group on the 14th and 28th days after surgery. The percentage of mineralization tissues of new bone area on the 14th and 28th days after injection were (27.73±5.93)% and (46.53±3.66)% in the DFO group, and (11.99±2.02)% and (31.98±4.22)% in the control group. The percentage of mineralization tissues in the DFO group was significantly higher than that of the control group at each time point (P<0.001). The relative expression of HIF-1α in the DFO group compared with the control group was 2.86±0.48, 1.32±0.26, 1.32±0.32, 1.28±0.38 and 1.05±0.34 on the 5th, 7th, 10th, 14th and 28th days, with significant expression difference on the 5th day (P<0.01). Conclusion: Use of DFO in bone defects promotes vascularization and osteogenesis in the defect area, and maintains the protein activity of HIF-1α temporarily.

Key words: Deferoxamine, Vascularization, Osteogenesis, Hypoxia inducible factor 1, alpha subunit

CLC Number: 

  • R318.08

Figure 1

SD rats skull critical size defect modelA critical size defect of skull was made and the periosteum was kept complete."

Figure 2

Immunohistochemistry staining images of the vessels marker CD31 (n=3) Yellow arrow indicates the examples of vascular tissue, “B” marks the defect border or the edge of new bone. DFO, deferoxamine mesylate."

Table 1

Counting of vessel numbers in the DFO group and control group"

Post-operation days/d Control group ($\overline{x}$±s) DFO group ($\overline{x}$±s) t P
5 18.75±6.63 30.40±12.15 2.439 0.027
7 19.13±2.80 62.00±17.87 6.671 <0.001
10 51.35±16.21 73.43±15.63 4.349 <0.001
14 27.18±7.32 40.00±7.84 3.660 0.002
28 30.88±13.43 48.71±11.64 2.727 0.017

Figure 3

HE staining (A) and Masson staining (B) images of the bone defect area (n=3) New bone is circulated by yellow and marked with “NB”. DFO, deferoxamine mesylate."

Table 2

Measuring of percentages of mineralized tissue area"

Post-operation days/d Control group ($\overline{x}$±s) DFO group ($\overline{x}$±s) t P
14 (11.99±2.02)% (27.73±5.93)% 5.967 <0.001
28 (31.98±4.22)% (46.53±3.66)% 6.045 <0.001

Figure 4

Expression of HIF-1α (DAB ×200, n=3) Examples of HIF-1α protein expression positively stained in brown is indicated with yellow arrow. DFO, deferoxamine mesylate; HIF-1α, hypoxia inducible factor 1α."

Table 3

Relative expression of HIF-1α (fold change)"

Post-operation
days/d		 Relative expression of
HIF-1α (fold change, $\overline{x}$±s)		 t P
5 2.86±0.48 7.660 0.002
7 1.32±0.26 2.131 0.083
10 1.32±0.32 2.007 0.069
14 1.28±0.38 1.454 0.121
28 1.05±0.34 0.196 0.438
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