Piezo1-mediated mechanotransduction regulates diabetic osteoporosis and hyperglycemia via low-intensity pulsed ultrasound.

Abstract

This study investigates the effects and mechanism by which low-intensity pulsed ultrasound (LIPUS) regulates osteoporosis and hyperglycemia in mice with type 1 diabetes mellitus (T1DM). The mice were randomly divided into four groups: normal control (NC), T1DM mice (DM), T1DM mice treated with insulin (DM + INS), and T1DM mice treated with LIPUS (DM + LIPUS). The DM + INS group served as a positive control for the study. The DM + LIPUS group received LIPUS treatment (80 mW cm^-2, 20 min daily) on the quadriceps femoris for 6 weeks. The results show that LIPUS improves the mechanical properties, morphological characteristics, and bone microstructure and alleviate hyperglycemia in the T1DM mice. In addition, knockout of Piezo1 using CRISPR-Cas9 was performed in MC3T3-E1 cells (Piezo1^-/-) to verify the role of LIPUS during treatment. The cell experiments showed that LIPUS improved proliferation, osteogenic differentiation capabilities, and cytoskeletal morphology, while significantly reducing the extracellular glucose level of MC3T3-E1 cells in a high glucose medium. All these results indicate that Piezo1-mediated mechanotransduction is closely related to the alleviation of osteoporosis and hyperglycemia in T1DM mice treated with LIPUS. LIPUS showed comparable efficacy to insulin in reducing the severity of osteoporosis and lowering hyperglycemia in T1DM mice. This therapy effectively alleviated symptoms (including osteoporosis and hyperglycemia) in T1DM mice without insulin injections. These findings suggest that LIPUS therapy could serve as an adjunct method to conventional diabetes treatment in T1DM.