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

Biochem Biophys Res Commun. 2017 Jul 8;488(4):634-640. doi: 10.1016/j.bbrc.2016.11.011. Epub 2016 Nov 5.

Abstract

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.

Keywords: Osteoclastogenesis; Osteocytes; Sympathetic nervous system; β-adrenoceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Isoproterenol / pharmacology
  • Mice
  • Osteocytes / drug effects
  • Osteocytes / metabolism*
  • Osteogenesis*
  • RANK Ligand / biosynthesis*
  • RAW 264.7 Cells
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / metabolism*
  • Signal Transduction*

Substances

  • RANK Ligand
  • Receptors, Adrenergic, beta
  • Isoproterenol