The role of beta 2 adrenergic receptors in osteocytes
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Osteocytes are the most abundant cell type in bone. Although our understanding of the function of osteocytes has progressed over the last decade, these cells remain the least understood cell in bone. Osteocytes are considered to be orchestrators of bone remodeling, mineral homeostasis, and hematopoiesis. The sympathetic nervous system (SNS) regulates almost every system in the body including bone. It is known that SNS suppresses bone formation but the mechanism is still not fully elucidated. Beta 2 adrenergic receptor (β2AR) is a G-protein coupled receptor that, upon binding to norepinephrine, activates the stimulatory subunit of the heterotrimeric G protein (Gαs) and the enzyme adenylate cyclase. The function of β2AR in osteocytes has not been studied. Therefore, the goal of this study is to delineate the role of β2AR signaling in osteocytes. To investigate that, an osteocyte-like cell line (Ocy454) was used. Ocy454 cells were treated with three different agents: norepinephrine (NE), isoproterenol (ISO), and butoxamine. Knock down of β2AR was achieved by using short hairpin RNA. Consequently, treatment with norepinephrine (NE) was done as well as fluid flow shear stress (FFSS) experiment. Taken together, this study shows that osteocytes do express β2AR and that β1AR and β2AR are almost equally expressed in osteocytes. Secondly, we have demonstrated that upon treatment of Ocy454 with NE and isoproterenol, there is a significant upregulation of Rankl, whereas Sost is not significantly regulated. Lastly, preliminary data suggest that β2AR might be involved in osteocyte’s mechanosensation.