Inhibitory effects of low intensity pulsed ultrasound on osteoclastogenesis induced in vitro by breast cancer cells

Abstract

BackgroundBone tissue is one of the main sites for breast metastasis; patients diagnosed with advanced breast cancer mostly develop bone metastasis characterized by severe osteolytic lesions, which heavily influence their life quality. Low Intensity Pulsed Ultrasound (LIPUS) is a form of mechanical energy able to modulate various molecular pathways both in cancer and in health cells.The purpose of the present study was to evaluate for the first time, the ability of LIPUS to modulate osteolytic capability of breast cancer cells.MethodsTwo different approaches were employed: a) Indirect method -conditioned medium obtained by MDA-MB-231 cell line treated or untreated with LIPUS was used to induce osteoclast differentiation of murine macrophage Raw264.7 cell line; and b) Direct method -MDA-MB-231 were co-cultured with Raw264.7 cells and treated or untreated with LIPUS.ResultsLIPUS treatment impaired MDA-MB-231 cell dependentosteoclast differentiation and produced a reduction of osteoclast markers such as Cathepsin K, Matrix Metalloproteinase 9 and Tartrate Resistant Acid Phosphatase, suggesting its role as an effective and safe adjuvant in bone metastasis management.ConclusionLIPUS treatment could be a good and safety therapeutic adjuvant in osteolyitic bone metastasis not only for the induction properties of bone regeneration, but also for the reduction of osteolysis.

Low‐intensity pulsed ultrasound protects subchondral bone in rabbit temporomandibular joint osteoarthritis by suppressing TGF‐β1/Smad3 pathway

“…38,39 A recent study by Carina V, showed that LIPUS stimulation produced a reduction in osteoclast markers such as Cathepsin K, matrix metalloproteinase 9, and TRAP, suggesting that LIPUS treatment could promote bone regeneration and reduce osteolysis. 40 The results of this study showed that LIPUS reduced the protein expression of Cathepsin K and inhibited osteoclast activity. These differences in research results may be related to the experimental environment and parameters of LIPUS stimulation.…”

Low-intensity Pulsed Ultrasound regulates alveolar bone homeostasis in experimental Periodontitis by diminishing Oxidative Stress

“…Low-intensity pulsed ultrasound (LIPUS) is a non-invasive ultrasound technique that transmits low frequency and low-intensity sound waves into tissues as acoustic pressure waves 6 , 7 . Conversion of mechanical signals emanating from these pressure waves to biochemical responses results in downstream effects 8 . Multiple experiments have demonstrated that LIPUS modulates bone tissue regeneration and accelerates bone repair processes by upregulating bone specific genes and downregulating osteoclast differentiation 9 , 10 .…”

Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in Invasive Cancer Cells

“…Our previous work demonstrated that mechanosensory FUSstimulation generates a robust Ca 2+ signaling response which can be used to distinguish invasive from non-invasive cancer cells (Hwang et al, 2013;Weitz et al, 2017). Others have also demonstrated mechanosensory Ca 2+ signaling responses using non-focused US-stimulation in other contexts (Wood and Sehgal, 2015;Carina et al, 2018;Pan et al, 2018) as well as more general studies to clarify the physiological, cell biological and molecular mechanisms underlying mechanosensory dependent Ca 2+ signaling responses (Tyler et al, 2008;Castellanos et al, 2016;Liu et al, 2017;Maresca et al, 2018). Our results include several new findings that further clarify the mechanically responsive Ca 2+ signaling pathways and identify a new role for PANX1 in mediating the FUS-dependent responses.…”