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体外冲击波对大鼠软骨细胞和颞下颌关节骨关节炎的保护作用;体内 Tc-HDP SPECT 和体外 micro-CT 的临床前评估。

Protective effects of extracorporeal shockwave on rat chondrocytes and temporomandibular joint osteoarthritis; preclinical evaluation with in vivoTc-HDP SPECT and ex vivo micro-CT.

机构信息

Department of Nuclear Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.

Department of Conservative Dentistry, Ewha Womans University School of Medicine, Seoul, South Korea.

出版信息

Osteoarthritis Cartilage. 2019 Nov;27(11):1692-1701. doi: 10.1016/j.joca.2019.07.008. Epub 2019 Jul 16.

Abstract

OBJECTIVE

Extracorporeal shockwave therapy (ESWT) has been shown to have chondroprotective effects on arthritic diseases. We investigated the effects of ESWT on temporomandibular joint osteoarthritis (TMJOA) using rat chondrocytes and TMJOA rat models.

DESIGN

Cell viability and expression of pro-inflammatory cytokines, cartilage degradation, and apoptosis markers were measured in control, monosodium iodoacetate (MIA)-treated and ESWT plus MIA-treated chondrocytes in vitro, and intra-articular MIA injection (TMJOA) and ESWT on TMJOA rats in vivo. In vivoTc-hydroxymethylene diphosphonate (HDP) single-photon emission computerized tomography/computerized tomography (SPECT/CT) and ex-vivo micro-CT and histologic examinations were performed in rat models.

RESULTS

ESWT plus MIA-treated chondrocytes showed increased cell viability significantly (P = 0.007), while decreased genetic expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6); P < 0.001 for each] and cartilage degradation markers [matrix metalloproteinase-3 (MMP3), matrix metalloproteinase-13 (MMP13), and bone morphogenetic protein 7 (BMP7); P < 0.001 for each], and number of apoptotic cells (P < 0.001) compared to MIA-treated chondrocytes. Changes in cytochrome c and cleaved caspase-3 levels relative to procaspase-3 were decreased over MIA-treated chondrocytes. ESWT on TMJOA rat models was associated with a significant decrease in pro-inflammatory and cartilage degradation markers, as demonstrated by real-time PCR and immunohistochemistry stains (P < 0.001 for each). On Tc-HDP SPECT/CT, the ESWT group showed a significantly lower uptake ratio compared to the TMJOA group (P = 0.008). Micro-CT analysis revealed that the ESWT group showed improved structure and bone quality compared to the TMJOA control group.

CONCLUSIONS

ESWT was associated with a protective effect on cartilage and subchondral bone structures of TMJOA by reducing inflammation, cartilage degradation, and chondrocyte apoptosis.

摘要

目的

体外冲击波疗法(ESWT)已被证明对关节炎疾病具有软骨保护作用。我们通过体外培养的软骨细胞和 TMJOA 大鼠模型,研究了 ESWT 对颞下颌关节骨关节炎(TMJOA)的影响。

设计

在体外,通过测量对照、单碘乙酸盐(MIA)处理和 ESWT 加 MIA 处理的软骨细胞中的细胞活力和促炎细胞因子的表达、软骨降解和细胞凋亡标志物,以及关节内 MIA 注射(TMJOA)和体内 ESWT 对 TMJOA 大鼠的影响。在大鼠模型中进行体内 Tc-羟甲基二膦酸盐(HDP)单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)和体外 micro-CT 和组织学检查。

结果

与 MIA 处理的软骨细胞相比,ESWT 加 MIA 处理的软骨细胞的细胞活力显著增加(P=0.007),同时促炎细胞因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)]和软骨降解标志物[基质金属蛋白酶-3(MMP3)、基质金属蛋白酶-13(MMP13)和骨形态发生蛋白 7(BMP7)]的基因表达以及凋亡细胞的数量均显著降低(P<0.001)。与 MIA 处理的软骨细胞相比,细胞色素 c 和裂解的半胱天冬酶-3 与前半胱天冬酶-3 的相对水平降低。TMJOA 大鼠模型上的 ESWT 与实时 PCR 和免疫组织化学染色显示的促炎和软骨降解标志物的显著降低相关(P<0.001)。在 Tc-HDP SPECT/CT 上,ESWT 组与 TMJOA 组相比,摄取率显著降低(P=0.008)。Micro-CT 分析显示,与 TMJOA 对照组相比,ESWT 组的结构和骨质量得到改善。

结论

ESWT 通过减少炎症、软骨降解和软骨细胞凋亡,对 TMJOA 的软骨和软骨下骨结构具有保护作用。

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