Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model
Open Access
- 1 May 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (9), 3208
- https://doi.org/10.3390/ijms21093208
Abstract
It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed β-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the β-TCP + Sr group in the latter stage (day 40–60). VEGFR-2 activity increased in the + Sr group from days 0–15 but decreased and showed significantly less activity than the β-TCP and non-scaffold groups from days 40–60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the β-TCP group, whereas the percentage of osseous tissue formation in the β-TCP group was significantly higher than in the β-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.Keywords
This publication has 62 references indexed in Scilit:
- Accumulation of bone strontium measured by in vivo XRF in rats supplemented with strontium citrate and strontium ranelateBone, 2013
- Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An OverviewTissue Engineering, Part B: Reviews, 2011
- Infection, Inflammation, and Bone Regeneration: a Paradoxical RelationshipJournal of Dental Research, 2011
- The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosityActa Biomaterialia, 2010
- Micro-computed tomography assessment of fracture healing: Relationships among callus structure, composition, and mechanical functionBone, 2009
- Modulation of the Inflammatory Response for Enhanced Bone Tissue RegenerationTissue Engineering, Part B: Reviews, 2008
- The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritisArthritis Research & Therapy, 2008
- Resolution of inflammation: the beginning programs the endNature Immunology, 2005
- Strontium ranelate: a novel concept for the treatment of osteoporosisWiener klinische Wochenschrift, 2005
- Quantitative measurement of the splice variants 120 and 164 of the angiogenic peptide vascular endothelial growth factor in the time flow of fracture healing: a study in the ratCell and tissue research, 2002