Low Concentration of Sodium Butyrate from Ultrabraid+NaBu suture, Promotes Angiogenesis and Tissue Remodelling in Tendon-bones Injury.
Sodium butyrate (NaBu), a form of short-chain fatty acid (SCFA), acts classically as a potent anti-angiogenic agent in tumour angiogenesis models, some authors demonstrated that low concentrations of NaBu may contribute to healing of tendon-bone injury in part at least through promotion of tissue remodelling. Here, we investigated the effects of low-range concentrations of NaBu using in vitro and in vivo assays using angiogenesis as the primary outcome measure and the mechanisms through which it acts. We demonstrated that NaBu, alone or perfused from the UltraBraid+NaBu suture was pro-angiogenic at very low-range doses promoting migration, tube formation and cell invasion in bovine aortic endothelial cells (BAECs). Furthermore, cell exposure to low NaBu concentrations increased expression of proteins involved in angiogenic cell signalling, including p-PKCβ1, p-FAK, p-ERK1/2, p-NFκβ, p-PLCγ1 and p-VEGFR2. In addition, inhibitors of both VEGFR2 and PKCβ1 blocked the angiogenic response. In in vivo assays, low concentrations of NaBu induced neovascularization in sponge implants in mice, evidenced by increased numbers of vessels and haemoglobin content in these implants. The findings in this study indicate that low concentrations of NaBu could be an important compound to stimulate angiogenesis at a site where vasculature is deficient and healing is compromised.
School of Healthcare Science, GMBC, Manchester Metropolitan University, Manchester, United Kingdom.
Donghui
D
Liu
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
Silvia Passos
SP
Andrade
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
Pollyana Ribeiro
PR
Castro
Smith &Nephew Research Centre, York Science, Park Heslington, York, UK.
John
J
Treacy
School of Healthcare Science, GMBC, Manchester Metropolitan University, Manchester, United Kingdom.
Jason
J
Ashworth
School of Healthcare Science, GMBC, Manchester Metropolitan University, Manchester, United Kingdom.|University of Medicine and Pharmacy, Tirgu Mures, Romania.
Mark
M
Slevin
D000818:Animals; D001842:Bone and Bones / Q000098:blood supply* / Q000293:injuries; D020148:Butyric Acid / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D064546:Protein Kinase C beta / Q000378:metabolism; D013537:Sutures; D013708:Tendon Injuries / Q000503:physiopathology; D013710:Tendons / Q000098:blood supply*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020148:Butyric Acid; D040301:Vascular Endothelial Growth Factor Receptor-2; D064546:Protein Kinase C beta
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