Relationship of gene expression in the injured human meniscus to body mass index: a biologic connection between obesity and osteoarthritis.
Relationship of gene expression in the injured human meniscus to body mass index: a biologic connection between obesity and osteoarthritis.
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DOI：
10.1002/art.38643
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发表时间：
2014-08
影响因子：
13.3
通讯作者：
Brophy, Robert H.
中科院分区：
文献类型：
--
作者：
Rai, Muhammad Farooq;Patra, Debabrata;Sandell, Linda J.;Brophy, Robert H.
较高的身体质量指数（BMI）会增加半月板损伤和膝骨关节炎（OA）的风险。然而，肥胖是否以及如何影响半月板生物学尚不清楚。我们分析了受伤人类半月板的转录组基因表达谱，以验证半月板基因表达特征与患者BMI相关的假设。半月板标本采集自接受关节镜半月板部分切除术的患者。转录组范围内的基因表达分析，然后通过QuantiGene Plex试验验证选定的转录本。分析基因表达与BMI的相关性以及3种BMI类别[瘦（LN； BMI= 18.5-24.9 kg/m2），超重（OW； BMI=25.0 - 29.9 kg/m2），肥胖（OB; BMI bb0 30.0 kg/m2）]的相对折叠变化，并通过计算探索综合功能分类。OB/OW比较的差异最大（565个转录本），其次是OB/LN（280个转录本）和OW/LN（125个转录本）比较。表达转录物的聚类分析证实了生物再现性。差异调控转录本是重要的功能分类。与氧转运、钙离子结合和细胞稳态相关的转录本随着BMI升高，而与细胞外基质沉积、细胞迁移和氨基葡萄糖代谢过程相关的转录本则受到抑制。虽然这些功能分类可能在软骨/半月板稳态中发挥关键作用，但细胞外基质沉积的失败和钙离子结合的增加可能有助于半月板损伤后OA的发展。我们的研究结果表明OB/OW类型的基因表达差异大于OW/LN类型。这可能表明有一个体重阈值，受伤的半月板对增加的BMI有严重的反应。bmi相关的基因表达变化为半月板损伤在肥胖患者OA发展中的作用提供了一个合理的解释。
Higher body mass index (BMI) increases the risk of meniscus injury and knee osteoarthritis (OA). However, it is unknown if and how obesity affects meniscus biology. We analyzed transcriptome-wide gene expression profiles of injured human menisci to test the hypothesis that meniscal gene expression signatures relate to patient BMI. Meniscus samples were collected from patients undergoing arthroscopic partial meniscectomy. Transcriptome-wide analysis of gene expression followed by validation of selected transcripts by QuantiGene Plex assay was performed. Correlations of gene expression with BMI and relative fold-changes in three BMI categories [lean (LN; BMI=18.5–24.9 kg/m2), overweight (OW; BMI=25.0−29.9 kg/m2), obese (OB; BMI>30.0 kg/m2)] were analyzed and integrated functional classifications were probed computationally. OB/OW comparison resulted in the largest set of differences (565-transcripts) followed by OB/LN (280-transcripts) and OW/LN (125-transcripts) comparisons. Biologic reproducibility was confirmed by cluster analysis of expressed transcripts. Differentially regulated transcripts represented important functional classifications. Transcripts associated with oxygen-transport, calcium-ion-binding, and cell-homeostasis were elevated with BMI while those related to extracellular-matrix-deposition, cell-migration, and glucosamine-metabolic-processes were repressed. While these functional classifications may play key roles in cartilage/meniscus homeostasis, failure of extracellular-matrix-deposition and increase in calcium-ion-binding likely contribute to OA development following meniscal injury. Our results indicate greater differences in gene expression between OB/OW category rather than OW/LN category. This may indicate that there is a weight-threshold at which injured meniscus responds severely to increased BMI. BMI-related changes in gene expression present a plausible explanation for the role of meniscal injury in OA development among obese patients.
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