title: Systemic administration of an antagomir designed to inhibit miR-92, a regulator of angiogenesis, failed to modulate skeletal anabolic response to mechanical loading.
abstract: The goal of this study is to evaluate if promotion of angiogenesis by systemic treatment with an antagomir against miR-92a, a well established inhibitor of angiogenesis, will maximize the benefits of exercise on bone. Ten week old female C57BL6/J mice were subjected to two weeks of external load by four point bending. During the first week of mechanical loading (ML), mice were injected (2.7 mg/kg of bodyweight) with antagomir against miR-92 or control antagomir (3 alternate days via retro-orbital). No difference in tissues weights (heart, kidney, liver) were found in mice treated with miR-92 vs. control antagomir suggesting no side effects. Two weeks of ML increased tibia TV, BV/TV and density by 6-15 %, as expected, in the control antagomir treated mice. Similar increases in the above parameters (7-16 %) were also seen in mice treated miR-92 antagomir. Administration of miR-92 antagomir was effective in reducing levels of mir-92 in heart, liver and skeletal muscle and in contrast, expression levels of two other microRNA's miR-93 and miR-20a remain constant, thus suggesting specificity of the antagomir used. Surprisingly, we failed to detect significant changes in the expression levels of vascular genes (VEGF, CD31 and Tie2) in heart, liver or skeletal muscle. Based on these findings, we conclude that systemic administration of antagomir against miR-92 while reduced expression levels of miR-92 in the tissues; it did not significantly alter either angiogenic or osteogenic response, thus suggesting possible redundancy in miR-92 regulation of angiogenesis.
authors.affiliation: Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sengul
authors.forename: R
authors.initials: R
authors.lastname: Santisuk
authors.forename: W
authors.initials: W
authors.lastname: Xing
authors.forename: C
authors.initials: C
authors.lastname: Kesavan
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D009929:Organ Size / Q000502:physiology; D005082:Physical Exertion; D010812:Physical Stimulation; D012313:RNA / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed
chemical_list: D035683:MicroRNAs; C541873:Mirn92 microRNA, mouse; D012313:RNA