Investigating the role of B1AR in Osteoclasts through Dobutamine Treatments
Document Type
Oral Presentation
Department
Biological Sciences
Abstract
Previous studies have established that the Beta-2 adrenergic receptor, paired with increased sympathetic nervous system output, plays a role in promoting osteoclastogenesis and bone resorption. However, the role of Beta-1 adrenergic receptor (β1AR) in bone metabolism remains largely unclear. Researchers have observed that β1AR antagonists, commonly used to treat heart conditions, have led to increased bone mineral density in clinical settings. On the contrary, studies conducted in our lab using genetic manipulation of β1AR have found otherwise. Through the utilization of a conditional β1AR knockout mouse model, we observed that in females, bone resorption marker Acp5 was increased while formation markers decreased in bone tissue. An increase in osteoclastogenesis and decrease in bone formation in the absence of β1AR, would lead to a bone loss phenotype. Analysis of the bone microarchitecture is underway to gain a better understanding of the phenotype. To explore the role of β1AR further, we are utilizing the selective β1AR agonist, dobutamine, to test the direct effects of β1AR in osteoclasts. We hypothesize that the activation of β1AR will lead to a decrease in osteoclast activity. Various techniques will be used to analyze these cultures, including RNA analysis as well as TRAP+ staining and Cell Proliferation assays. We aim to fully characterize the differentiation and activity of osteoclasts in vitro, as well as determine if activation of β1AR impacts osteoclast differentiation and activity. Future work involves the replication of these in vitro experiments as well as dosing mice with β1AR agonists and antagonists to explore the changes in bone phenotypes.
Investigating the role of B1AR in Osteoclasts through Dobutamine Treatments
Previous studies have established that the Beta-2 adrenergic receptor, paired with increased sympathetic nervous system output, plays a role in promoting osteoclastogenesis and bone resorption. However, the role of Beta-1 adrenergic receptor (β1AR) in bone metabolism remains largely unclear. Researchers have observed that β1AR antagonists, commonly used to treat heart conditions, have led to increased bone mineral density in clinical settings. On the contrary, studies conducted in our lab using genetic manipulation of β1AR have found otherwise. Through the utilization of a conditional β1AR knockout mouse model, we observed that in females, bone resorption marker Acp5 was increased while formation markers decreased in bone tissue. An increase in osteoclastogenesis and decrease in bone formation in the absence of β1AR, would lead to a bone loss phenotype. Analysis of the bone microarchitecture is underway to gain a better understanding of the phenotype. To explore the role of β1AR further, we are utilizing the selective β1AR agonist, dobutamine, to test the direct effects of β1AR in osteoclasts. We hypothesize that the activation of β1AR will lead to a decrease in osteoclast activity. Various techniques will be used to analyze these cultures, including RNA analysis as well as TRAP+ staining and Cell Proliferation assays. We aim to fully characterize the differentiation and activity of osteoclasts in vitro, as well as determine if activation of β1AR impacts osteoclast differentiation and activity. Future work involves the replication of these in vitro experiments as well as dosing mice with β1AR agonists and antagonists to explore the changes in bone phenotypes.
