Open AccessStimulating angiogenesis mitigates the unloading‐induced reduction in osteogenesis in early‐stage bone repair in rats
Author(s) -
Matsumoto Takeshi,
Sato Shota
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12335
Subject(s) - angiogenesis , reduction (mathematics) , medicine , bone healing , bioinformatics , dentistry , surgery , biology , geometry , mathematics
Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine ( DFO ) mitigates the unloading‐induced reduction in early‐stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading ( HU ), HU and DFO administration ( DFOHU ), or weight bearing ( WB ) for 5 or 10 days ( HU 5/10, DFOHU 5/10, WB 5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide‐based contrast agent. Taking advantage of its absorption discontinuity at the K‐absorption edge, vascular and bone images in the drill‐hole defects were acquired by synchrotron radiation subtraction CT . Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU 5 and 42% smaller in HU 10 than in WB 5/10. The bone segment densities (B.Seg) were 97% smaller in HU 5 and 141% larger in HU 10 than in WB 5/10, and bone thickness (B.Th) was 38% smaller in HU 10 than in WB 10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU 10 than in WB 10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20–30, 30–40, and >40 μ m were smaller in HU 10 than in WB 10, and V.Seg in the diameter range >40 μ m was smaller in HU 10 than in WB 10. In contrast, there was no difference in B.Vf between DFOHU 5/10 and WB 5/10 and in V.Vf between DFOHU 10 and WB 10, though B.Seg remained 86% smaller in DFOHU 5 and 94% larger in DFOHU 10 than in WB 5/10, and B.Th and V.D were 23% and 14% lower in DFOHU 10 than in WB 10. Vessel size‐specific V.Vf in the diameter ranges 10–20 and 20–30 μ m was larger in DFOHU 5 than in HU 5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading.