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骨关节炎中髌下脂肪垫来源间充质干细胞的基因表达调控

Modulation of Gene Expression in Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Osteoarthritis.

作者信息

Bravo Beatriz, Argüello Jose Manuel, Gortazar Arancha R, Forriol Francisco, Vaquero Javier

机构信息

1 CEU-San Pablo University School of Medicine, IMMA, Boadilla del Monte, Madrid, Spain.

2 Department of Orthopaedic Surgery, Hospital Parla, Madrid, Spain.

出版信息

Cartilage. 2018 Jan;9(1):55-62. doi: 10.1177/1947603516686144. Epub 2017 Jan 10.

DOI:10.1177/1947603516686144
PMID:29156945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5724676/
Abstract

Aim In the osteoarthritis (OA) disease, all structures of the joint are involved. The infrapatellar Hoffa fat pad is rich in macrophages and granulocytes, which also represents a source of adipose mesenchymal progenitor cells (ASC) cells. In our study, we analyze how OA affects the ability of ASC-derived from Hoffa's fat pad to differentiate into chondrocytes. Material and methodology We took knee Hoffa's pad samples and adipose tissue from the proximal thigh from 6 patients diagnosed with severe OA and from another 6 patients with an anterior cruciate ligament (ACL) rupture without OA. From all the patients, we took subcutaneous adipose tissue from the thigh, as the control group. Samples of synovial fluid (SF) were also extracted. The gene expression was analyzed by real-time quantitative polymerase chain reaction. Results PTH1R and MMP13 expression during chondrogenic differentiation were similar between OA and ACL groups, while the expression of OPG, FGF2, TGFβ, MMP3 were significantly lower in the OA group. Exposure of differentiated ASC to OA SF induced an increase in the expression of OPG, PTH1R, and MMP13 and a decrease in the expression of FGF2 in cell culture of the ACL group. However, expression of none of these factors was altered by the OA synovial fluid in ASC cells of the OA group. Conclusion OA of the knee also affects the mesenchymal stem cells of Hoffa fat, suggesting that Hoffa fat is a new actor in the OA degenerative process that can contribute to the origin, onset, and progression of the disease.

摘要

目的 在骨关节炎(OA)疾病中,关节的所有结构都会受累。髌下Hoffa脂肪垫富含巨噬细胞和粒细胞,也是脂肪间充质祖细胞(ASC)的一个来源。在我们的研究中,我们分析了OA如何影响源自Hoffa脂肪垫的ASC分化为软骨细胞的能力。

材料和方法 我们从6例诊断为重度OA的患者以及另外6例无OA的前交叉韧带(ACL)断裂患者身上获取膝关节Hoffa垫样本和大腿近端的脂肪组织。从所有患者身上采集大腿皮下脂肪组织作为对照组。还提取了滑液(SF)样本。通过实时定量聚合酶链反应分析基因表达。

结果 在软骨形成分化过程中,OA组和ACL组的PTH1R和MMP13表达相似,而OA组中OPG、FGF2、TGFβ、MMP3的表达明显较低。在ACL组的细胞培养中,将分化的ASC暴露于OA滑液会导致OPG、PTH1R和MMP13表达增加,FGF2表达降低。然而,OA组ASC细胞中的OA滑液并未改变这些因子中的任何一个的表达。

结论 膝关节OA也会影响Hoffa脂肪的间充质干细胞,这表明Hoffa脂肪是OA退变过程中的一个新因素,可能对该疾病的起源、发病和进展有影响。

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