Beta-adrenergic signaling affect osteoclastogenesis via osteocytic MLO-Y4 cells' RANKL production

The sympathetic nervous system play a pivotal role in bone remodeling through β-adrenoceptor (β-AR). However, it is not well documented whether the β-adrenoceptor pathway has the potential to influence osteocytes. In this study, cell viability, the expression of β-AR subtypes, enzymes of catecholamine synthesis or degradation, bone-related gene and protein in osteocytic MLO-Y4 cells were investigated by β-adrenergic stimulation. Isoproterenol (ISO) promoted RANKL to OPG expression in osteocytes, as well as osteoclasts formation in osteocytes-RAW264.7 cell co-cultures but not RAW264.7 cell monoculture. The ISO-stimulated effect was enhanced in β1-AR antagonist pretreatment, but was rescued by blocking β2-AR. The results indicate that β1-and β2-AR play reciprocal roles on MLO-Y4 cells in the regulation of osteoclastogenesis, and osteocyte β-adrenergic signaling might be a new valuable therapy for bone disease.