Lee Wonsae, Georgas Elias, Komatsu David E, Qin Yi-Xian
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Department of Orthopaedics and Rehabilitation, Stony Brook University, Stony Brook, NY, USA.
J Orthop Translat. 2023 Dec 20;44:9-18. doi: 10.1016/j.jot.2023.09.002. eCollection 2024 Jan.
The aim of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) in a post-traumatic osteoarthritis (OA) rat model and .
Thirty-eight male, four-month-old Sprague Dawley rats were randomly assigned to Sham, Sham + US, OA, and OA + US. Sham surgery was performed to serve as a negative control, and anterior cruciate ligament transection was used to induce OA. Three days after the surgical procedures, Sham + US and OA + US animals received daily LIPUS treatment, while the rest of the groups received sham ultrasound (US) signals. Behavioral pain tests were performed at baseline and every week thereafter. After 31 days, the tissues were collected, and histological analyses were performed on knees and innervated dorsal root ganglia (DRG) neurons traced by retrograde labeling. Furthermore, to assess the activation of osteoclasts by LIPUS treatment, RAW264.7 cells were differentiated into osteoclasts and treated with LIPUS.
Joint degradation in cartilage and bone microarchitecture were mitigated in OA + US compared to OA. OA + US showed improvements in behavioral pain tests. A significant increase of large soma-sized DRG neurons was located in OA compared to Sham. In addition, a greater percentage of large soma-sized innervated neurons were calcitonin gene-related peptide-positive. Daily LIPUS treatment suppressed osteoclastogenesis , which was confirmed via histological analyses and mRNA expression. Finally, lower expression of netrin-1, a sensory innervation-related protein, was found in the LIPUS treated cells.
Our findings demonstrate that early intervention using LIPUS treatment has protective effects from the progression of knee OA, including reduced tissue degradation, mitigated pain characteristics, improved subchondral bone microarchitecture, and less sensory innervation. Furthermore, daily LIPUS treatment has a suppressive effect on osteoclastogenesis, which may be linked to the suppression of sensory innervation in OA.
This study presents a new potential for early intervention in treating OA symptoms through the use of LIPUS, which involves the suppression of osteoclastogenesis and the alteration of DRG profiles. This intervention aims to delay joint degradation and reduce pain.
本研究旨在探讨低强度脉冲超声（LIPUS）对创伤后骨关节炎（OA）大鼠模型的影响。
38只4月龄雄性Sprague Dawley大鼠被随机分为假手术组、假手术 + 超声组、骨关节炎组和骨关节炎 + 超声组。进行假手术作为阴性对照，采用前交叉韧带横断术诱导骨关节炎。手术操作3天后，假手术 + 超声组和骨关节炎 + 超声组动物接受每日LIPUS治疗，其余组接受假超声（US）信号。在基线时及之后每周进行行为疼痛测试。31天后，收集组织，对膝关节和通过逆行标记追踪的支配背根神经节（DRG）神经元进行组织学分析。此外，为评估LIPUS治疗对破骨细胞激活的影响，将RAW264.7细胞分化为破骨细胞并进行LIPUS处理。
与骨关节炎组相比，骨关节炎 + 超声组的软骨和骨微结构中的关节退变得到缓解。骨关节炎 + 超声组在行为疼痛测试中有所改善。与假手术组相比，骨关节炎组中大型躯体大小的DRG神经元显著增加。此外，大型躯体大小的支配神经元中降钙素基因相关肽阳性的比例更高。每日LIPUS治疗抑制破骨细胞生成，这通过组织学分析和mRNA表达得到证实。最后，在接受LIPUS治疗的细胞中发现神经纤毛蛋白-1（一种与感觉神经支配相关的蛋白）的表达较低。
我们的研究结果表明，使用LIPUS治疗进行早期干预对膝关节OA的进展具有保护作用，包括减少组织退变、减轻疼痛特征、改善软骨下骨微结构和减少感觉神经支配。此外，每日LIPUS治疗对破骨细胞生成具有抑制作用，这可能与OA中感觉神经支配的抑制有关。
本研究展示了通过使用LIPUS对OA症状进行早期干预的新潜力，这涉及抑制破骨细胞生成和改变DRG特征。这种干预旨在延缓关节退变并减轻疼痛。
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