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.
Academy for Engineering and Technology, Fudan University, Shanghai 200433, China.
Ultrasonics. 2023 Jul;132:106973. doi: 10.1016/j.ultras.2023.106973. Epub 2023 Feb 27.
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.
低强度脉冲超声（LIPUS）已被证明是治疗骨质疏松症的有效技术。为了更好地激活与骨形成相关的标志物，促进成骨的不同阶段，并进一步增强超声的治疗效果，本研究采用脉冲调频超声（pFMUS）治疗因 4-乙烯环己烯二氧化物（VCD）注射导致卵巢功能衰竭的骨质疏松症小鼠。将 8 周龄健康雌性 C57BL/6J 小鼠随机分为四组：假手术（S）、VCD 对照组（V）、VCD+LIPUS（VU）和 VCD+pFMUS（VFU）。VU 和 VFU 组分别接受 LIPUS 和 pFMUS 治疗。通过血清分析、微计算机断层扫描（micro-CT）、力学测试和苏木精和伊红（HE）染色来评估超声的治疗效果。通过定量逆转录 PCR（qRT-PCR）和 Western blot 分析来探讨超声对骨质疏松症的作用机制。结果表明，在骨微结构和骨强度方面，pFMUS 可能比传统 LIPUS 具有更好的治疗效果。此外，pFMUS 可以通过激活磷酸肌醇 3 激酶/蛋白激酶 B（PI3K/Akt）通路促进骨形成，并通过增加骨保护素/核因子 κB 配体受体激活剂（OPG/RANKL）比值来减缓骨吸收。当了解超声对骨质疏松症的调节机制并建立基于多频超声的骨质疏松症新治疗方案时，本研究具有积极的预后意义。
