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

Abstract

Long cytoplasmic processes of osteocytes orchestrate bone activity by integration of biochemical and mechanical signals and regulate load-induced bone adaptation. Low-Intensity Pulsed Ultrasound (LIPUS) is a clinically used technique for fracture healing that delivers mechanical impulses to the damaged bone tissue in a non-invasive and non-ionizing manner. The mechanism of action of LIPUS is still controversially discussed in the scientific community. In this study, the effect of focused LIPUS (FLIPUS) on the survival of starved MLO-Y4 osteocytes was investigated in vitro. Osteocytes stimulated for 10 min with FLIPUS exhibited extended dendrites, which formed frequent connections to neighboring cells and spanned longer distances. The sonicated cells displayed thick actin bundles and experienced increase in expression of connexin 43 (Cx43) proteins, especially on their dendrites, and E11 glycoprotein, which is responsible for the elongation of cellular cytoplasmic processes. After stimulation, expression of cell growth and survival genes as well as genes related to cell–cell communication was augmented. In addition, cell viability was improved after the sonication, and a decrease in ATP release in the medium was observed. In summary, FLIPUS mitigated apoptosis of starved osteocytes, which is likely related to the formation of the extensive dendritic network that ensured cell survival.

ATP-induced cell death: a novel hypothesis for osteoporosis

“…It is widely believed that the dysplasia of osteoblasts and osteoclasts is a factor leading to osteoporosis (Xiao et al, 2023). Estrogen depletion, inflammatory responses, and immune dysregulation [including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)] in conjunction with disturbances in calcium ion homeostasis can independently or synergistically trigger apoptotic, autophagic, and necroptotic processes in bone cells, culminating in the onset of osteoporosis (Wang et al, 2023b;Cui et al, 2023;Feng et al, 2023;Jeong et al, 2023;Puts et al, 2023;Xiao et al, 2023;Zhu et al, 2023). Furthermore, aberrant activities of osteoclasts and multinucleated macrophages result in the release of acidifying substances and bone resorption-related proteases, contributing to bone degradation and subsequent osteoporosis (Bao et al, 2023) Importantly, cell death pathways are also implicated in secondary osteoporosis, encompassing conditions such as diabetic osteoporosis, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis.…”