Shang Jin, Wang Honggang, Fan Xin, Shangguan Lei, Liu Huan
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
Mol Med Rep. 2016 Aug;14(2):1389-96. doi: 10.3892/mmr.2016.5359. Epub 2016 Jun 2.
Low back pain is a prevalent disease, which leads to suffering and disabilities in a vast number of individuals. Degenerative disc diseases are usually the underlying causes of low back pain. However, the pathogenesis of degenerative disc diseases is highly complex and difficult to determine. Current therapies for degenerative disc diseases are various. In particular, cell-based therapies have proven to be effective and promising. Our research group has previously isolated and identified the cartilage endplate‑derived stem cells. In addition, alternative splicing is a sophisticated regulatory mechanism, which greatly increases cellular complexity and phenotypic diversity of eukaryotic organisms. The present study continued to investigate alternative splicing events in osteogenic differentiation of cartilage endplate‑derived stem cells. An Affymetrix Human Transcriptome Array 2.0 was used to detect splicing changes between the control and differentiated samples. Additionally, molecular function and pathway analysis were also performed. Following rigorous bioinformatics analysis of the data, 3,802 alternatively spliced genes were identified, and 10 of these were selected for validation by reverse transcription‑polymerase chain reaction. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analysis also revealed numerous enriched GO terms and signaling pathways. To the best of our knowledge, the present study is the first to investigate alternative splicing mechanisms in osteogenic differentiation of stem cells on a genome‑wide scale. The illumination of molecular mechanisms of stem cell osteogenic differentiation may assist the development novel bioengineered methods to treat degenerative disc diseases.
腰痛是一种常见疾病,导致大量个体遭受痛苦并出现残疾。椎间盘退变疾病通常是腰痛的根本原因。然而,椎间盘退变疾病的发病机制高度复杂且难以确定。目前针对椎间盘退变疾病的治疗方法多种多样。特别是,基于细胞的治疗方法已被证明是有效且有前景的。我们的研究小组此前已分离并鉴定了软骨终板来源的干细胞。此外,可变剪接是一种复杂的调控机制,它极大地增加了真核生物的细胞复杂性和表型多样性。本研究继续探讨软骨终板来源干细胞成骨分化过程中的可变剪接事件。使用Affymetrix人类转录组阵列2.0检测对照样本和分化样本之间的剪接变化。此外,还进行了分子功能和通路分析。在对数据进行严格的生物信息学分析后,鉴定出3802个可变剪接基因,并从中选择了10个通过逆转录-聚合酶链反应进行验证。基因本体(GO)和京都基因与基因组百科全书通路分析也揭示了大量富集的GO术语和信号通路。据我们所知,本研究首次在全基因组范围内研究干细胞成骨分化中的可变剪接机制。阐明干细胞成骨分化的分子机制可能有助于开发治疗椎间盘退变疾病的新型生物工程方法。