Piezoelectric Microvibration Mitigates Estrogen Loss-Induced Osteoporosis and Promotes Piezo1, MicroRNA-29a, and Wnt3a Signaling in Osteoblasts

Abstract

Biophysical stimulation alters bone-forming cell activity, bone formation and remodeling. The effect of piezoelectric microvibration stimulation (PMVS) intervention on osteoporosis development remains uncertain. We investigated whether 60 Hz, 120 Hz, and 180 Hz PMVS (0.05 g, 20 min/stimulation, 3 stimulations/week for 4 consecutive weeks) intervention affected bone integrity in ovariectomized (OVX) mice or osteoblastic activity. PMVS (120 Hz)-treated OVX mice developed fewer osteoporosis conditions, including bone mineral density loss and trabecular microstructure deterioration together with decreased serum resorption marker CTX-1 levels, as compared to control OVX animals. The biomechanical strength of skeletal tissue was improved upon 120 Hz PMVS intervention. This intervention compromised OVX-induced sparse trabecular bone morphology, osteoblast loss, osteoclast overburden, and osteoclast-promoting cytokine RANKL immunostaining and reversed osteoclast inhibitor OPG immunoreactivity. Osteoblasts in OVX mice upon PMVS intervention showed strong Wnt3a immunoreaction and weak Wnt inhibitor Dkk1 immunostaining. In vitro, PMVS reversed OVX-induced loss in von Kossa-stained mineralized nodule formation, Runx2, and osteocalcin expression in primary bone-marrow stromal cells. PMVS also promoted mechanoreceptor Piezo1 expression together with increased microRNA-29a and Wnt3a expression, whereas Dkk1 rather than SOST expression was repressed in MC3T3-E1 osteoblasts. Taken together, PMVS intervention promoted Piezo1, miR-29a, and Wnt signaling to upregulate osteogenic activity and repressed osteoclastic bone resorption, delaying estrogen deficiency-induced loss in bone mass and microstructure. This study highlights a new biophysical remedy for osteoporosis.

Magnetic particles for triggering insulin release in INS-1E cells subjected to a rotating magnetic field

“…Indeed, these channels have been shown to be activated by distinct mechanical stimuli, all of them inducing plasma membrane deformations, including membrane stretch due to hypotonic treatment, shear stress, hydrostatic pressure, compression, ultrasound or piezoelectric microvibration. 27,29–33 This would allow the release of insulin, which could therefore contribute to the treatment of diabetes. Still, in contrast to all the other sources of the mechanical stimulation of pancreatic β-cells that have been described so far, the magneto-mechanical treatment proposed here can be finely tuned to be delivered to β-cells only, because Fe 20 Ni 80 particles can be easily functionalized to promote targeted delivery.…”

Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease

“…A 3-point bending protocol with a 6-mm jag span was employed to assess the breaking forces of femoral diaphysis using the SHIMADZU EZ-SX Material Test System (Shimadzu Corporation, Kyoto, Japan), as described in our previous study (Wu et al 2021 ). The displacement speed of the stainless-steel load (50 N) was set at 2 cm/min.…”

MicroRNA-loaded biomaterials for osteogenesis

“…The Wnt pathway is also regulated by miRNAs acting on pathway inhibitors, such as GSK-3β and DKK-1 ( Wu et al, 2021 ). Upstream activation of Dvl leads to the dissolution of the downstream β-catenin degradation complexes, including APC and GSK-3β, to avoid the ubiquitination of β-catenin by complexes and transport to the proteasome for degradation ( Ma et al, 2020a ; Yang et al, 2020 ).…”

“…DKK family proteins are cysteine-rich secreted proteins that bind the Kremen protein and Wnt co-receptor LRP5 to form trimers to mediate intracellular phagocytosis, reduce Wnt receptors on the cell surface, and antagonize Wnt signal transduction ( Zhang et al, 2017b ). MiR-29a was found to target DKK-1 to activate osteogenic gene expression and matrix mineralization, and promote bone formation ( Wu et al, 2021 ). MiR-335-5p and miR-217 can also directly bind to DKK1 mRNA3′-UTR to activate Wnt signaling ( Zhang et al, 2017b ; Dai et al, 2019 ).…”

“…Osteoprotegerin (OPG), also known as the osteoclastogenesis inhibitor, is likewise produced by osteoblasts, which combine with RANK to interfere with RANKL localization in cells and inhibit osteoclastogenesis ( Marycz et al, 2021 ; Wu et al, 2021 ). MiR-27a interferes with the localization of RANKL in cells by increasing OPG transcription, regulating the RANKL/OPG ratio, reducing osteoclast formation, and promoting bone remodeling ( Guo et al, 2019 ).…”