ABSTRACT
Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2(LacZ/+) reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2(LacZ/LacZ) mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2(LacZ/LacZ) mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice.
Subject(s)
Ear, External/physiopathology , Skin/physiopathology , Wnt Signaling Pathway/physiology , Wound Healing/physiology , Animals , Axin Protein/genetics , Axin Protein/metabolism , Ear, External/injuries , Ear, External/metabolism , Epidermis/metabolism , Epidermis/physiopathology , Gene Expression , Hair Follicle/metabolism , Immunohistochemistry , Liposomes , Mice , Mice, Transgenic , Reverse Transcriptase Polymerase Chain Reaction , Skin/injuries , Skin/metabolism , Time Factors , Wnt Signaling Pathway/genetics , Wnt3A Protein/genetics , Wnt3A Protein/metabolism , Wound Healing/genetics , beta-Galactosidase/genetics , beta-Galactosidase/metabolismABSTRACT
Wnt signaling is activated by wounding and participates in every subsequent stage of the healing process from the control of inflammation and programmed cell death, to the mobilization of stem cell reservoirs within the wound site. In this review we summarize recent data elucidating the roles that the Wnt pathway plays in the injury repair process. These data provide a foundation for potential Wnt-based therapeutic strategies aimed at stimulating tissue regeneration.
Subject(s)
Apoptosis/physiology , Inflammation/physiopathology , Models, Biological , Regeneration/physiology , Wnt Signaling Pathway/physiology , Wound Healing/physiology , Animals , Humans , Species SpecificityABSTRACT
Mechanisms underlying the vascular differentiation of human bone marrow stromal cells (HBMSCs) and their contribution to neovascularisation are poorly understood. We report the essential role of cell density-induced signals in directing HBMSCs along endothelial or smooth muscle lineages. Plating HBMSCs at high density rapidly induced Notch signaling, which initiated HBMSC commitment to a vascular progenitor cell population expressing markers for both vascular lineages. Notch also induced VEGF-A, which inhibited vascular smooth muscle commitment while consolidating differentiation to endothelial cells with cobblestone morphology and characteristic endothelial markers and functions. These mechanisms can be exploited therapeutically to regulate HBMSCs during neovascularisation.
