Profiling MicroRNA Expression in Bovine Articular Cartilage and Implications for Mechanotransduction
Profiling MicroRNA Expression in Bovine Articular Cartilage and Implications for Mechanotransduction
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DOI：
10.1002/art.24678
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发表时间：
2009-08-01
影响因子：
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通讯作者：
Reddi, A. Hari
中科院分区：
文献类型：
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作者：
Dunn, Walter;DuRaine, Grayson;Reddi, A. Hari
Objective.关节软骨是一种无血管组织，具有精确的极性和组织，包括3个不同的功能区：表层、中层和深层。每个区域都有不同的基因表达模式，在关节软骨发育和维持中发挥特定作用。微小RNA（microRNA，miRNA）是一类小的非编码基因产物，在决定细胞分化和功能方面起着重要的调控作用。本研究的目的是验证我们的假设，即在不同的关节软骨区以及不同水平的负重应力区域之间的miRNA表达谱是独特的。我们采用miRNA微阵列技术结合定量逆转录-聚合酶链反应（RT-PCR），鉴定了牛关节软骨中在不同功能区以及股骨内侧髁前部负重区和后部非负重区（分别为M1和M4）差异表达的miRNA。我们鉴定了miRNA-221。和miR-222作为差异表达的miRNA亚组的一部分，其在前M1更大负重位置的关节软骨中上调。此外，与直接从完整天然软骨中测定的水平相比，miR-126、miR-145和miR-335在组织培养的单层软骨细胞中下调。总之，miR-222在关节软骨中的表达模式在负重的前内侧髁中高于后非负重的内侧髁。因此，miR-222可能是关节软骨机械转导途径的潜在调节剂。这些数据表明，miRNA在维持关节软骨稳态，因此关节软骨组织工程和再生医学的目标。
Objective. Articular cartilage is an avascular tissue with precise polarity and organization comprising 3 distinct functional zones: the surface, middle, and deep zones. Each zone has a different gene expression pattern that plays a specific role in articular cartilage development and maintenance. MicroRNA (miRNA) are small noncoding gene products that play an important regulatory role in determining cell differentiation and function. The purpose of this study was to test our hypothesis that miRNA expression profiles in the different articular cartilage zones as well as between regions subjected to different levels of weight-bearing stresses are unique.Methods. Using an miRNA microarray approach in conjunction with quantitative reverse transcription-polymerase chain reaction, we identified miRNA in bovine articular cartilage that were differentially expressed in the different functional zones and in the anterior weight-bearing and posterior non-weight-bearing regions of the medial femoral condyle (M1 and M4, respectively).Results. We identified miRNA-221. and miR-222 as part of a subset of differentially expressed miRNA that were up-regulated in articular cartilage in the anterior, M1, greater weight-bearing location. Additionally, miR-126, miR-145, and miR-335 were down-regulated in monolayers of tissue-cultured chondrocytes as compared with levels determined directly from intact native cartilage.Conclusion. In conclusion, miR-222 expression patterns in articular cartilage are higher in the weight-bearing anterior medial condyle as compared with the posterior non-weight-bearing medial condyle. Thus, miR-222 might be a potential regulator of an articular cartilage mechanotransduction pathway. These data implicate miRNA in the maintenance of articular cartilage homeostasis and are therefore targets for articular cartilage tissue engineering and regenerative medicine.