Department of Oral Anatomy and Physiology, School of Stomatology, China Medical University, Shenyang, China.
Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, China.
J Orthop Res. 2020 Nov;38(11):2505-2512. doi: 10.1002/jor.24628. Epub 2020 Feb 26.
Transforming growth factor β1(TGF-β1)/Smad3 pathway promotes the pathological progression of subchondral bone in osteoarthritis. The aim of this study is to determine the effect of low-intensity pulsed ultrasound (LIPUS) on the pathological progression and TGF-β1/Smad3 pathway of subchondral bone in temporomandibular joint osteoarthritis (TMJOA). Rabbit TMJOA model was established by type II collagenase induction. The left joint in this model was continuously stimulated with LIPUS for 3 and 6 weeks (1 MHz; 30 mW/cm ) for 20 min/day. The morphological and histological features of subchondral bone were respectively examined by microcomputed tomography and Safranin-O staining. The number of osteoclasts was quantitatively assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry and Western blot analysis were conducted to evaluate the protein expression of Cathepsin K and TGF-β1/Smad3 pathway. The results indicated that LIPUS could improve the trabecular microstructure and histological characteristics of subchondral bone in rabbit TMJOA. It also suppressed abnormal subchondral bone resorption and activation of TGF-β1/Smad3 pathway, characterized by the number of osteoclasts, protein expression levels of Cathepsin K, TGF-β1, type II TGFβ receptor, and phosphorylated Smad3 (pSmad3) were decreased. In conclusion, LIPUS promoted the quality of subchondral bone by suppressing osteoclast activity and TGF-β1/Smad3 pathway in rabbit TMJOA.
转化生长因子β1（TGF-β1）/Smad3 通路促进骨关节炎软骨下骨的病理进展。本研究旨在探讨低强度脉冲超声（LIPUS）对颞下颌关节骨关节炎（TMJOA）软骨下骨病理进展及 TGF-β1/Smad3 通路的影响。采用 II 型胶原酶诱导法建立兔 TMJOA 模型。对模型左侧关节进行持续 LIPUS 刺激，刺激时间分别为 3 周和 6 周（1MHz；30mW/cm ），每天 20min。采用 microCT 和番红 O 染色分别观察软骨下骨的形态和组织学特征。采用抗酒石酸酸性磷酸酶染色定量评估破骨细胞数量。采用免疫组织化学和 Western blot 分析评估组织蛋白酶 K 和 TGF-β1/Smad3 通路的蛋白表达。结果表明，LIPUS 可改善兔 TMJOA 软骨下骨的小梁微结构和组织学特征。同时抑制了软骨下骨的异常吸收和 TGF-β1/Smad3 通路的激活，表现为破骨细胞数量、组织蛋白酶 K、TGF-β1、II 型 TGFβ 受体和磷酸化 Smad3（pSmad3）的蛋白表达水平降低。综上所述，LIPUS 通过抑制兔 TMJOA 中破骨细胞活性和 TGF-β1/Smad3 通路，促进软骨下骨质量的改善。
