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在骨关节炎实验模型中,与间充质脂肪来源干细胞植入相关的光生物调节能否减弱基质金属蛋白酶的表达并减少II型胶原蛋白的降解?

Can photobiomodulation associated with implantation of mesenchymal adipose-derived stem cells attenuate the expression of MMPs and decrease degradation of type II collagen in an experimental model of osteoarthritis?

作者信息

Stancker Tatiane Garcia, Vieira Stella Souza, Serra Andrey Jorge, do Nascimento Lima Rafael, Dos Santos Feliciano Regiane, Silva José Antônio, Dos Santos Solange Almeida, Dos Santos Vieira Marcia Ataize, Simões Maíra Cecília Brandão, Leal-Junior Ernesto Cesar, de Tarso Camillo de Carvalho Paulo

机构信息

Postgraduate Program in Rehabilitation Sciences, Universidade Nove de Julho (UNINOVE), Rua Vergueiro 235, São Paulo, SP, Brazil.

Postgraduate Program in Cardiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

出版信息

Lasers Med Sci. 2018 Jul;33(5):1073-1084. doi: 10.1007/s10103-018-2466-0. Epub 2018 Mar 8.

Abstract

This study aimed to determine whether photobiomodulation therapy (PBMT) could improve the bioavailability and chondroprotective benefits of mesenchymal stem cells injected into the knees of rats used as an experimental model of osteoarthritis (OA) as well as reduce the expression of matrix metalloproteinases (MMPs) and degradation of type II collagen (COL2-1) in the cartilage. Adipose-derived stem/stromal cells (ADSCs) were collected from three male Fischer 344 rats and characterized by flow cytometry. Fifty female Fischer 344 rats were distributed into five groups of 10 animals each. These groups were as follows: control, OA, OA PBMT, OA ADSC, and OA ADSC PBMT. OA was induced in the animals using a 4% papain solution. Animals from the OA ADSC and OA ADSC PBMT groups received an intra-articular injection of 10 × 10 ADSCs and were treated with PBMT by irradiation (wavelength: 808 nm, power: 50 mW, energy: 42 J, energy density: 71.2 J/cm, spot size: 0.028). Euthanasia was performed 7 days after the first treatment. The use of PBMT alone and the injection of ADSCs resulted in downregulation of pro-inflammatory cytokines and MPs in cartilage compared to the OA group. PBMT and ADSCs caused upregulation of tissue inhibitors of MPs 1 and 2 and mRNA and protein expression of COL2-1 in cartilage compared to the OA group. The intra-articular injection of ADSCs and PBMT prevented joint degeneration resulting from COL2-1 degradation and modulated inflammation by downregulating cytokines and MMPs in the OA group.

摘要

本研究旨在确定光生物调节疗法(PBMT)是否能提高注入大鼠膝关节的间充质干细胞的生物利用度和软骨保护作用,该大鼠作为骨关节炎(OA)的实验模型,同时减少软骨中基质金属蛋白酶(MMPs)的表达和II型胶原蛋白(COL2-1)的降解。从三只雄性Fischer 344大鼠中收集脂肪来源的干/基质细胞(ADSCs),并通过流式细胞术进行表征。将50只雌性Fischer 344大鼠分成五组,每组10只动物。这些组如下:对照组、OA组、OA+PBMT组、OA+ADSC组和OA+ADSC+PBMT组。使用4%木瓜蛋白酶溶液在动物中诱导OA。OA+ADSC组和OA+ADSC+PBMT组的动物接受10×10的ADSCs关节内注射,并通过照射进行PBMT治疗(波长:808nm,功率:50mW,能量:42J,能量密度:71.2J/cm,光斑尺寸:0.028)。在首次治疗后7天实施安乐死。与OA组相比,单独使用PBMT和注射ADSCs导致软骨中促炎细胞因子和MMPs下调。与OA组相比,PBMT和ADSCs导致软骨中MMPs组织抑制剂1和2以及COL2-1的mRNA和蛋白质表达上调。关节内注射ADSCs和PBMT可预防因COL2-1降解导致的关节退变,并通过下调OA组中的细胞因子和MMPs来调节炎症。

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