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Oral administration of bovine lactoferrin accelerates the healing of fracture in ovariectomized rats

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Lactoferrin has recently been reported for its potent bone growth effects. However, the effects of lactoferrin on the healing process of fragility fracture have not yet been studied, so the purpose of this study is to investigate whether oral administration of lactoferrin can promote the fracture healing in an OVX animal model.

Materials and methods

Three months after bilateral ovariectomy, all rats underwent unilateral tibial osteotomy and were then randomly divided into control group and bovine lactoferrin (bLF) group. At 4 and 8 weeks post-fracture, animals were sacrificed, and the fractured tibiae and serum samples were collected for evaluation.

Results

Our results showed that bLF treatment not only accelerated the bone growth at an early stage of OPF healing but also shortened the remolding process of OPF healing. When compared to control group, bLF treatment induced a significant rise in callus BMD (by 35.0% at 4 weeks and by 39.7% at 8 weeks; both p < 0.05) consistent with enhanced biomechanical strength of the callus, with ultimate force increased by 3.39-fold at 4 weeks (p < 0.05) and 1.95-fold at 8 weeks (p < 0.05). Besides, bLF administration resulted in a substantial increase in serum levels of BALP and a significant decrease in serum levels of TRAP 5b and TNF-α. Moreover, both the RANKL/OPG mRNA ratio and the expression of TNF-α in the callus of bLF-treated group were markedly lower than those in the control group.

Conclusions

At a dose of 85mg/kg/day orally administrated bLF potently promoted the bone healing following tibial fracture in OVX rats.

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Acknowledgements

This study was supported by grants from The National Natural Science Foundation of China (No. 81600832), Chongqing Research Program of Basic Research and Frontier Technology (cstc2019jcyj-msxmX0455), Project Supported by Scientific and Technological Research Program of Chongqing Municipal Education Commission (No. KJQN201900406, KJQN201902804), Project Supported by Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016 (No. CXTDG201602006) and Project Supported by Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, College of Stomatology, Chongqing Medical University, Chongqing, 400016, China

    Wenyang Li, Jing Hu & Ping Ji

  2. Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, China

    Wenyang Li, Jing Hu & Ping Ji

  3. Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China

    Wenyang Li, Jing Hu & Ping Ji

  4. Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Yuzhong District, Yixueyuan Road 1#, Chongqing, 400016, China

    Ying Zhu

  5. Faculty of Medical Technology, Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China

    Shisheng Zhu

  6. Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing, 401331, China

    Shisheng Zhu

Authors
  1. Wenyang Li
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  2. Jing Hu
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  3. Ping Ji
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Contributions

WL contributed to conception, design, data acquisition, analysis, and interpretation, drafted the manuscript; JH contributed to data acquisition, analysis, and interpretation, drafted and critically revised the manuscript; PJ and SZ contributed to conception and design, and critically revised the manuscript; YZ contributed to conception, design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript.

Corresponding author

Correspondence to Ying Zhu.

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774_2020_1105_MOESM1_ESM.jpg

Supplementary file1. Fig.1S. Histological examination of the tibial metaphyseal at 12 weeks after bilateral ovariectomy (H&E staining; × 100): a OVX group, b Sham group. The scale bar represents 100 μm. c DXA examination of the tibial metaphyseal at 12 weeks after bilateral ovariectomy, n = 5 specimens/group. Data are expressed as mean ± SD, error bars in the figure indicate SD. ★p < 0.05 vs. Sham group. d Fracture was generated by a transverse osteotomy at the proximal one third of the tibiae (JPG 840 kb)

774_2020_1105_MOESM2_ESM.jpg

Supplementary file2. Fig.2S. The scheme of our study design. OVX ovariectomized, DXA dual dual-energy x-ray absorptiometry, RT-PCR reverse transcription-polymerase chain reaction (JPG 818 kb)

774_2020_1105_MOESM3_ESM.jpg

Supplementary file3. Fig.3S. Values of BMD (a) and ultimate force (b) of the contralateral tibial metaphysic, n = 6 specimens/group. Data are expressed as mean ± SD, error bars in the figure indicate SD. ★p < 0.05 vs. control group (JPG 653 kb)

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Li, W., Hu, J., Ji, P. et al. Oral administration of bovine lactoferrin accelerates the healing of fracture in ovariectomized rats. J Bone Miner Metab 38, 648–657 (2020). https://doi.org/10.1007/s00774-020-01105-1

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  • DOI: https://doi.org/10.1007/s00774-020-01105-1

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