Low-intensity pulsed ultrasound (LIPUS) and cell-to-cell communication in bone marrow stromal cells

Low-intensity pulsed ultrasound (LIPUS) is an established therapy for fracture repair and has been used widely in the clinics, but its underlying mechanism of action remains unclear. The aim of the current research was to determine the effect of LIPUS on gap junctional cell-to-cell intercellular communication in rat bone marrow stromal cells (BMSC) in vitro and to determine whether the ability of BMSCs to communicate by gap junctions would affect their response to LIPUS. Single or daily-multiple LIPUS treatment at 1.5 MHz, 30 mW/cm2, for 20 min was applied to BMSC. We demonstrated that BMSC form functional gap junctions and single LIPUS treatment significantly increased the intracellular dye transfer between BMSC. In addition, activated phosphorylation of ERK1/2 and p38 by LIPUS stimulation was diminished when cells were treated with a gap junction inhibitor 18β-glycyrrhetinic acid (18β). We further demonstrated that 18β diminished the significant increase in alkaline phosphatase activity following LIPUS stimulation. These results suggest a potential role of gap junctional cell-to-cell intercellular communication on the effects of LIPUS in BMSC.

Research highlights
► LIPUS-stimulated intercellular calcein dye transfer in bone marrow stromal cells.
► 18β inhibits LIPUS-stimulated intercellular calcein dye transfer.
► 18β inhibits LIPUS-stimulated phosphorylation of p38, ERK1/2, and ALP activity.