Low-intensity pulsed ultrasound/nanomechanical force generators enhance osteogenesis of BMSCs through microfilaments and TRPM7

Abstract

Background Low-intensity pulsed ultrasound (LIPUS) has been reported to accelerate fracture healing, but the mechanism is unclear and its efficacy needs to be further optimized. Ultrasound in combination with functionalized microbubbles has been shown to induce local shear forces and controllable mechanical stress in cells, amplifying the mechanical effects of LIPUS. Nanoscale lipid bubbles (nanobubbles) have high stability and good biosafety. However, the effect of LIPUS combined with functionalized nanobubbles on osteogenesis has rarely been studied. Results In this study, we report cyclic arginine-glycine-aspartic acid-modified nanobubbles (cRGD-NBs), with a particle size of ~ 500 nm, able to actively target bone marrow mesenchymal stem cells (BMSCs) via integrin receptors. cRGD-NBs can act as nanomechanical force generators on the cell membrane, and further enhance the BMSCs osteogenesis and bone formation promoted by LIPUS. The polymerization of actin microfilaments and the mechanosensitive transient receptor potential melastatin 7 (TRPM7) ion channel play important roles in BMSCs osteogenesis promoted by LIPUS/cRGD-NBs. Moreover, the mutual regulation of TRPM7 and actin microfilaments promote the effect of LIPUS/cRGD-NBs. The extracellular Ca2 + influx, controlled partly by TRPM7, could participated in the effect of LIPUS/cRGD-NBs on BMSCs. Conclusions The nanomechanical force generators cRGD-NBs could promote osteogenesis of BMSCs and bone formation induced by LIPUS, through regulation TRPM7, actin cytoskeleton, and intracellular calcium oscillations. This study provides new directions for optimizing the efficacy of LIPUS for fracture healing, and a theoretical basis for the further application and development of LIPUS in clinical practice.

Focused Low-Intensity Pulsed Ultrasound (FLIPUS) Mitigates Apoptosis of MLO-Y4 Osteocyte-like Cells

“…The stress induced by mechanical forces results in the formation of thick actin bundles, which was also confirmed in this study after the FLIPUS stimulation ( Figure 7 a,b). The polymerization of actin fibers after ultrasound stimulation is in agreement with previous reports [ 32 , 47 ]. The expression of vinculin, which is an important linker in the focal adhesion complex, bridging actin with integrin receptors bound to the surrounding matrix, was not affected by the stimulation.…”

Ag2O‐TiO2‐NTs enhance osteogenic activity in vitro by modulating TNF‐α/β‐catenin signaling in bone marrow‐derived mesenchymal stem cells

“…Zhang et al uncovered that the addition of magnesium ions throughout the bone tissue engineering process is beneficial to the bone formation ability of BMSCs (Xiong et al, 2020;Zhang et al, 2019). Yao et al discovered that the osteogenic potential of BMSCs could be enhanced by nanomicrofilaments (Yao et al, 2022). These investigations revealed that biomaterials might increase the therapeutic efficiency of BMSCs.…”

“…Yao et al. discovered that the osteogenic potential of BMSCs could be enhanced by nano‐microfilaments (Yao et al., 2022). These investigations revealed that biomaterials might increase the therapeutic efficiency of BMSCs.…”

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

“…In MC3T3-E1 cells, both receptors appear to be functional in the osteoblastic mechano-transduction that results in reduced proliferation [ 66 ]. TRPM7 is also a common target for mechanical loading to stimulate bone formation, as results obtained in various models suggest [ 67 , 68 , 69 ]. TRPM7 is critically important in bone formation [ 70 ].…”