Otto Aufranc Award: Identification of Key Molecular Players in the Progression of Hip Osteoarthritis Through Transcriptomes and Epigenetics.
Otto Aufranc Award: Identification of Key Molecular Players in the Progression of Hip Osteoarthritis Through Transcriptomes and Epigenetics.
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奥托·奥夫兰克奖：通过转录组学和表观遗传学确定髋骨关节炎进展中的关键分子因素
DOI：
10.1016/j.arth.2022.03.013
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发表时间：
2022-07
影响因子：
3.5
通讯作者：
Clohisy, John C.
中科院分区：
文献类型：
--
作者：
Pascual-Garrido, Cecilia;Kamenaga, Tomoyuki;Brophy, Robert H.;Shen, Jie;O'Keefe, Regis J.;Clohisy, John C.
本研究旨在：（1）比较cam-FAI（早期）和继发于cam-FAI的晚期OA（晚期）中关节软骨的转录组谱，（2）通过髋关节OA进展期间人软骨样本中DNA甲基化酶DNMT 3B、DNMT 1和DNMT 3A以及过氧化物酶体增殖物激活受体γ（PPARγ）的表达研究表观遗传变化。从22名患者（9名早期FAI和13名晚期FAI）的前外侧头颈连接处（撞击区）收集全层软骨样本。进行RNA测序和体外软骨培养，并进行组织学分析和PPARγ和DNMT 3B的免疫组织化学染色。RT-PCR验证目的基因。在早期和晚期FAI之间鉴定出50个基因和42条通路的差异（倍数变化<-1.5或>1.5，P <0.01）。随着疾病的进展，PPARγ和DNMT 3B逐渐受到抑制。因此，疾病进展诱导DNMT 1/3A的表达。通过在全基因组水平上比较早期和晚期髋关节退行性变中的综合基因表达，确定了早期和晚期疾病的不同转录组谱沿着髋关节OA进展的关键分子贡献者。保留内源性PPARγ可能具有延缓或预防髋关节OA的治疗潜力。
This study aimed: (1) to compare the transcriptome profile of articular cartilage in cam-FAI (early stage) to advanced OA secondary to cam-FAI (late stage) and (2) to investigate epigenetic changes through the expression of DNA methylation enzymes DNMT3B, DNMT1, and DNMT3A and peroxisome proliferator-activated receptor gamma (PPARγ) in human cartilage samples during the progression of hip OA. Full-thickness cartilage samples were collected from the anterolateral head-neck junction (impingement zone) of 22 patients (9 early-FAI and 13 late-FAI). RNA sequencing and in vitro cartilage cultures with histological analysis and immunohistochemistry staining for PPARγ and DNMT3B were performed. Target gene validation was confirmed with RT-PCR. Fifty genes and 42 pathways were identified differentially between early and late-FAI (fold change <−1.5 or >1.5, P < .01). PPARγ and DNMT3B were gradually suppressed with disease progression. Contrarily, disease progression induced expression of DNMT1/3A. By comparing comprehensive gene expression in early and late stage hip degeneration at the whole-genome level, distinct transcriptome profiles for early and late stage disease were identified along with key molecular contributors to the progression of hip OA. Preservation of endogenous PPARγ may have therapeutic potential to delay or prevent hip OA.
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Clohisy, John C.
影响因子：
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作者：
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通讯作者：
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