Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model
- 1 July 2015
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Clinical Orthopaedics and Related Research
- Vol. 473 (7), 2383-2393
- https://doi.org/10.1007/s11999-015-4270-5
Abstract
Lactoferrin, an iron-binding glycoprotein which belongs to the transferrin family, has been shown to promote bone growth. However, reports regarding effects of lactoferrin on bone regeneration during distraction osteogenesis are limited. Our study was designed to investigate the effect of bovine lactoferrin treatment on bone formation of the distracted callus. We asked whether bovine lactoferrin enhances bone formation of the distraction callus as determined by (1) radiographic and histologic appearances; (2) dual-energy x-ray absorptiometry (DXA) analysis of bone mineral composition and bone mineral density; (3) micro-CT measures of trabecular architecture; and (4) biomechanical strength of the healing bone. Additionally, serology, reverse transcription (RT)-PCR, and immunohistochemistry were used to explore the possible mechanisms of bovine lactoferrin use on bone formation during distraction osteogenesis. Unilateral tibial osteodistraction was performed on 80 New Zealand White rabbits with a distraction rate of 1 mm per day for 10 days. Animals then were divided randomly into two groups: (1) vehicle and (2) bovine lactoferrin. At 4 and 8 weeks after completion of distraction, the animals were sacrificed. Lengthened tibias and serum samples were obtained and subjected to radiologic, DXA, micro-CT, histologic, and biomechanical examinations, and serum, RT-PCR and immunohistochemical analyses. Radiologic, DXA, micro-CT, histologic, and biomechanical examinations indicated that bovine lactoferrin treatment not only accelerated bone formation at early stages of distraction osteogenesis but also promoted bone consolidation at late stages. The ultimate force of the distracted calluses was increased by 37% (118.8 ± 6.65 N in the lactoferrin group and 86.5 ± 5.47 N in the vehicle group; p < 0.001) and 84% (384.8 ± 18.4 N in the lactoferrin group and 209.0 ± 15.2 N in the vehicle group; p < 0.001) at 4 and 8 weeks, respectively. Moreover, serum analysis showed that bovine lactoferrin treatment significantly increased serum levels of bone alkaline phosphatase and decreased serum levels of tartrate resistant acid phosphatase 5b. In addition, RT-PCR and immunohistochemical analyses suggested that bovine lactoferrin treatment induced a lower receptor activator of nuclear factor-kappaB (RANK) ligand/osteoprotegerin (RANKL/OPG) ratio in the distracted callus. The results of our study suggest that bovine lactoferrin treatment could promote bone regeneration during distraction osteogenesis in the rabbit. The results indicate that the OPG/RANKL/RANK system might be a major mechanism for increased bone formation and decreased bone resorption in distraction osteogenesis with bovine lactoferrin treatment. Oral administration of bovine lactoferrin may provide a feasible approach for promoting osteogenesis during distraction osteogenesis.Keywords
This publication has 39 references indexed in Scilit:
- Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine ModelPLOS ONE, 2013
- Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathwayActa Pharmacologica Sinica, 2012
- bFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis in rabbitsBone, 2010
- Expression of Bone‐related Genes in Bone Marrow MSCs after Cyclic Mechanical Strain: Implications for Distraction OsteogenesisInternational Journal of Oral Science, 2009
- Immunomodulatory effects of lactoferrin on antigen presenting cellsBiochimie, 2009
- Bone consolidation is enhanced by rhBMP‐2 in a rabbit model of distraction osteogenesisJournal of Orthopaedic Research, 2002
- Effects of locally applied transforming growth factor-β1 on distraction osteogenesis in a rabbit limb-lengthening modelBone, 2000
- Problems, Obstacles, and Complications of Limb Lengthening by the Ilizarov TechniqueClinical Orthopaedics and Related Research, 1990
- Local Bone Transportation for Treatment of Intercalary Defects by the Ilizarov TechniqueClinical Orthopaedics and Related Research, 1989
- The Tension-Stress Effect on the Genesis and Growth of TissuesClinical Orthopaedics and Related Research, 1989