Pulsed frequency modulated ultrasound promotes therapeutic effects of osteoporosis induced by ovarian failure in mice

Xinyan Zhou; Shuxin Sun; Yuefu Chen; Chengcheng Liu; Dan Li; Qun Cheng; Min He; Ying Li; Kailiang Xu; Dean Ta

doi:10.1016/j.ultras.2023.106973

Pulsed frequency modulated ultrasound promotes therapeutic effects of osteoporosis induced by ovarian failure in mice

Ultrasonics. 2023 Jul:132:106973. doi: 10.1016/j.ultras.2023.106973. Epub 2023 Feb 27.

Authors

Xinyan Zhou¹, Shuxin Sun², Yuefu Chen², Chengcheng Liu³, Dan Li⁴, Qun Cheng⁵, Min He⁶, Ying Li⁷, Kailiang Xu⁸, Dean Ta⁹

Affiliations

¹ Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China; State Key Laboratory of Integrated Chips and Systems, Fudan University, Shanghai 201203, China.
² Academy for Engineering and Technology, Fudan University, Shanghai 200433, China.
³ Academy for Engineering and Technology, Fudan University, Shanghai 200433, China; State Key Laboratory of Integrated Chips and Systems, Fudan University, Shanghai 201203, China.
⁴ Department of Electronic Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China.
⁵ Department of Osteoporosis and Bone Disease, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
⁶ Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China.
⁷ Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China. Electronic address: yl@fudan.edu.cn.
⁸ Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China; Academy for Engineering and Technology, Fudan University, Shanghai 200433, China; State Key Laboratory of Integrated Chips and Systems, Fudan University, Shanghai 201203, China. Electronic address: xukl@fudan.edu.cn.
⁹ Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China; Academy for Engineering and Technology, Fudan University, Shanghai 200433, China; State Key Laboratory of Integrated Chips and Systems, Fudan University, Shanghai 201203, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: tda@fudan.edu.cn.

PMID: 36893552
DOI: 10.1016/j.ultras.2023.106973

Abstract

Low-intensity pulsed ultrasound (LIPUS) has been proved to be an effective technique for the treatment of osteoporosis. To better activate the bone formation-related markers, promote the different stages of osteogenesis, and further enhance the therapeutic effects of ultrasound, this study employed pulsed frequency modulated ultrasound (pFMUS) to treat mice with osteoporosis, which was caused by ovarian failure due to 4-vinylcyclohexene dioxide (VCD) injection. Healthy 8-week-old female C57BL/6J mice were randomly divided into four groups: Sham (S), VCD-control (V), VCD + LIPUS (VU), and VCD + pFMUS (VFU). VU and VFU groups were treated by LIPUS and pFMUS, respectively. Serum analysis, micro-computed tomography (micro-CT), mechanical testing and hematoxylin and eosin (HE) staining were performed to evaluate the therapeutic effects of ultrasound. Quantitative reverse-transcription PCR (qRT-PCR) and western blot analysis were used to explore the mechanism of ultrasound on osteoporosis. Results showed that pFMUS might have better therapeutic effects than traditional LIPUS in terms of bone microstructure and bone strength. In addition, pFMUS could promote bone formation by activating phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) pathway, and slow down bone resorption by increasing osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL) ratio. This study is of positive prognostic significance when understanding the mechanism of ultrasound regulation on osteoporosis and establishing novel treatment plan of osteoporosis by multi-frequency ultrasound.

Keywords: Low-intensity pulsed ultrasound; Osteoporosis; Ovarian failure; Pulsed frequency modulated ultrasound; Therapeutic effect.

MeSH terms

Animals
Female
Mice
Mice, Inbred C57BL
Osteoporosis* / therapy
Phosphatidylinositol 3-Kinases* / therapeutic use
Ultrasonic Waves
X-Ray Microtomography

Substances

Phosphatidylinositol 3-Kinases