The impact of Wnt signaling on hematopoietic stem cell aging and its influence on fracture repair

The impact of Wnt signaling on hematopoietic stem cell aging and its influence on fracture repair Tuyet Nguyen tuyet.nguyen@duke.edu Alman Laboratory Duke University Abstract Age-related fractures are a current problem with a high mortality rate and, as the United States aged population increases, will become a necessary problem to address in the near future. In order to find solutions for this impending dilemma, it is crucial to understand how bone heals and how this process changes with age. Under homeostatic conditions, bone health is maintained through dynamic relationships mediated in part by the Wnt signaling pathway, especially so during a fracture injury. Wnt signaling is also a known regulator in maintaining hematopoietic stem cells (HSCs) quality, but the role that HSCs play during a fracture injury has not been well explored. The bone marrow environment and the cells that make up the endosteal and perivascular niches are known to be important for postnatal HSC maintenance. However, during a fracture injury, both niches are disordered, and bone regeneration must proceed properly for the re-establishment of the microenvironment to restore the proper cellular HSC regulatory mechanisms. Our lab and others have shown that Wnt signaling is tightly regulated during the fracture healing process and that these signaling patterns become dysregulated with age. Nonetheless, it remains unclear how fracture injury- and age-specific changes to the Wnt pathway affect HSC differentiation and how this relationship in turn regulates fracture healing. This proposed work intends to address the gap in understanding of how HSCs affect the bone fracture repair process to develop better targeted therapeutics that best decrease fracture-related complications.