RGD Reference Report - Angiogenesis is required for stress fracture healing in rats. - Rat Genome Database

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Angiogenesis is required for stress fracture healing in rats.

Authors: Tomlinson, RE  McKenzie, JA  Schmieder, AH  Wohl, GR  Lanza, GM  Silva, MJ 
Citation: Tomlinson RE, etal., Bone. 2013 Jan;52(1):212-9. doi: 10.1016/j.bone.2012.09.035. Epub 2012 Oct 5.
RGD ID: 7248788
Pubmed: PMID:23044046   (View Abstract at PubMed)
PMCID: PMC3513671   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bone.2012.09.035   (Journal Full-text)

Although angiogenesis and osteogenesis are critically linked, the importance of angiogenesis for stress fracture healing is unknown. In this study, mechanical loading was used to create a non-displaced stress fracture in the adult rat forelimb. Fumagillin, an anti-angiogenic agent, was used as the water soluble analogue TNP-470 (25mg/kg) as well as incorporated into lipid-encapsulated alpha(v)beta(3) integrin targeted nanoparticles (0.25mg/kg). In the first experiment, TNP-470 was administered daily for 5 days following mechanical loading, and changes in gene expression, vascularity, and woven bone formation were quantified. Although no changes in vascularity were detected 3 days after loading, treatment-related downregulation of angiogenic (Pecam1) and osteogenic (Bsp, Osx) genes was observed at this early time point. On day 7, microCT imaging of loaded limbs revealed diminished woven bone formation in treated limbs compared to vehicle treated limbs. In the second experiment, alpha(v)beta(3) integrin targeted fumagillin nanoparticles were administered as before, albeit with a 100-fold lower dose, and changes in vascularity and woven bone formation were determined. There were no treatment-related changes in vessel count or volume 3 days after loading, although fewer angiogenic (CD105 positive) blood vessels were present in treated limbs compared to vehicle treated limbs. This result manifested on day 7 as a reduction in total vascularity, as measured by histology (vessel count) and microCT (vessel volume). Similar to the first experiment, treated limbs had diminished woven bone formation on day 7 compared to vehicle treated limbs. These results indicate that angiogenesis is required for stress fracture healing, and may have implications for inducing rapid repair of stress fractures.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Stress Fractures disease_progressionISOEng (Rattus norvegicus)7248788; 7248788protein:increased expression:ulna and vasculature (rat)RGD 
Stress Fractures disease_progressionIEP 7248788protein:increased expression:ulna and vasculature (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eng  (endoglin)

Genes (Mus musculus)
Eng  (endoglin)

Genes (Homo sapiens)
ENG  (endoglin)


Additional Information