Anti-resorption role of low-intensity pulsed ultrasound (LIPUS) during large-scale bone reconstruction using porous titanium alloy scaffolds through inhibiting osteoclast differentiation

Ti6Al4V biomaterials combine with low-intensity pulsed ultrasound (LIPUS) has been reported with great bone regeneration capacity. It is important to better understand how LIPUS benefits bone microenvironment to seek for target of therapeutic medicine. Osteoclast differentiation plays a crucial role in bone resorption. Recent advances in molecular biology have revealed that N6-methyladenosine (m6A) RNA modifications can modulate biological processes, but their role in bone biology, particularly in osteoclast differentiation, remains unclear. We aim to understand how LIPUS regulates bone microenvironment especially osteoclast formation during bone regeneration to provide new therapeutic options for preventing and delaying bone resorption, thus with better bone regeneration efficiency.1. LIPUS promoted bone ingrowth and bone maturity while inhibiting osteoclast formation within Ti6Al4V scaffolds in large-scale bone defect model. 2. LIPUS was found to inhibit osteoclast differentiation by decreasing the overall expression of osteoclast markers in vitro. 3. LIPUS decreases RNA m6A-modification level through upregulating FTO expression during osteoclast differentiation during. 4. Inhibiting FTO expression and function leads to less inhibition during osteoclast differentiation.LIPUS suppresses osteoclast differentiation during bone regeneration through reducing m6A modification of osteoclastic RNAs by up regulating FTO expression.