A Small Interfering RNA Targeting Lnk Using Atelocolagen as a Scaffold is Effective in Treatment of Unhealing Bone Fracture via Early Neovascularization

Unhealing Bone Fracture via Early Neovascularization + 1, 2 Y.Kawakami; 2 T.Matsumoto; 1 M.Ii; 1 A.Kawamoto; 1, 2 Y.Mifune; 1, 2 T.Fukui; 1, 2 T.Shoji; 2 R.Kuroda; 2 M.Kurosaka; 1 T.Asahara + 1 Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, Kobe, Japan. + 2 Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. [email protected] INTRODUCTION The therapeutic potential of hematopoietic stem/endothelial progenitor cells (HSCs/EPCs) for fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement in sites of fracture.(1) Lnk is expressed in hematopoietic cell lineages, and bone marrow (BM) cells of Lnk-deficient mice are superior in hematopoietic population of those of wildtype mice. Lnk has recently been proved an essential inhibitory signaling molecule in stem cell factor (SCF)-c-Kit signaling pathway for stem cell self-renewal demonstrating enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice.(2)(3) In terms of expanding clinical application, we therefore investigated the hypothesis that down regulation of Lnk signaling enhances regenerative response via vasculogenesis and osteogenesis in fracture healing.