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阿达木单抗阻断肿瘤坏死因子-α对骨关节炎大鼠模型关节软骨和软骨下骨的保护作用。

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis.

作者信息

Ma C H, Lv Q, Yu Y X, Zhang Y, Kong D, Niu K R, Yi C Q

机构信息

Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.

Department of Radiology, Tong Ji Hospital, Tong Ji University, Shanghai, CN.

出版信息

Braz J Med Biol Res. 2015 Oct;48(10):863-70. doi: 10.1590/1414-431X20154407. Epub 2015 Jul 31.

Abstract

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

摘要

我们旨在研究抗肿瘤坏死因子-α抗体(ATNF)对骨关节炎大鼠模型中软骨和软骨下骨的影响。24只大鼠被随机分为三组:假手术组(n = 8);前交叉韧带切断术(ACLT)+生理盐水(NS)组(n = 8);以及ACLT + ATNF组(n = 8)。ACLT + ATNF组的大鼠皮下注射ATNF(20μg / kg),持续12周,而ACLT + NS组的大鼠以相同剂量注射NS,持续12周。所有大鼠在手术后12周处死,并采集患侧膝关节的标本。进行苏木精和伊红染色、Masson三色染色以及Mankin评分评估,以评价软骨状态和软骨基质降解情况。采用基质金属蛋白酶(MMP)-13免疫组织化学法评估软骨分子代谢。运用骨组织形态计量学观察软骨下小梁微结构。与ACLT + NS组的大鼠相比,组织学和Mankin评分分析表明,ATNF治疗降低了软骨损伤的严重程度,并导致较低的Mankin评分。免疫组织化学和组织形态计量学分析显示,ATNF治疗减少了ACLT诱导的软骨下小梁微结构破坏,并降低了MMP-13表达。ATNF治疗可能通过降低MMP-13表达来延缓细胞外基质的降解。ATNF治疗可能通过改善软骨下骨结构和减少软骨基质降解来保护关节软骨。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd1f/4617111/60c4b4918a4a/1414-431X-bjmbr-48-10-00863-gf001.jpg

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