Research Projects

Beta-adrenoreceptors (?-ARs) are G protein-coupled receptors that mediate physiological responses to neurotransmitters. ?2- and ?3-AR signaling defects lead to various diseases, including aging, cardiovascular disorders, and cancer. Increased and decreased ?2- and ?3-AR signaling in bone marrow mesenchymal stromal cells (MSCs) cause hematopoietic stem cell (HSC) dysfunction in aging, with ?2- and ?3-AR signaling playing opposite roles in HSC migration. Osteopontin (OPN), produced by osteoblasts, MSCs, endothelial, and other cells, has multiple functions including ?2-AR signaling regulation. Reduced OPN due to osteoblast loss causes HSC dysfunction in aged mouse bone marrow. However, it is unclear whether there is a link between reduced OPN and imbalanced ?2- and ?3-AR signaling in bone marrow MSCs during aging. The current study aims to fill this gap in literature by hypothesizing that ?2- and ?3-AR signaling regulate each other via OPN, and that aging alters the balance between ?2- and ?-3AR signaling in bone marrow MSCs by downregulating OPN. Methods include stimulation of MS-5 human stromal cells with clenbuterol and BRL37344, and ?2- and ?3-AR signaling proteins in intracellular cAMP and ?-AR signaling proteins. The study also examines agonist-induced ?2- and ?3-AR signaling in OPN knockdown MS-5 cells, bone marrow and blood plasma expression of OPN in young and old WT mice, and OPN stimulation in young and old mouse MSCs.