Lee Jun-Ku, Yeo Hyunjeong, Choi Sujin, Kim Kyeong Mi, Kim Hannah, Lee Sung-Sahn, Lee Hyun Il, Jeong Younghoon, An Hyun-Ju, Lee Soonchul
Department of Orthopedic Surgery, National Health Insurance Service Ilsan Hospital, 100, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10444, Republic of Korea.
Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.
Sci Rep. 2024 Dec 28;14(1):31006. doi: 10.1038/s41598-024-82177-1.
Articular cartilage has a limited regenerative capacity, resulting in poor spontaneous healing of damaged tissue. Despite various scientific efforts to enhance cartilage repair, no single method has yielded satisfactory results. With rising drug development costs, drug repositioning has emerged as a viable alternative. This study aimed to identify a drug capable of improving cartilage defects by analyzing chondrogenesis-related microarray data from the Gene Expression Omnibus (GEO) public database. We utilized datasets GSE69110, GSE107649, GSE111822, and GSE116173 to identify genes associated with cartilage differentiation, employing StringTie for differential gene expression analysis and extracting drug data from the Drug-Gene Interaction database. Additionally, we aimed to verify the cartilage regeneration potential of the identified drug through experiments using cellular and animal models. We evaluated the effects of aripiprazole on adipose-derived mesenchymal stem cells (ADMSCs) and chondrocytes using qRT-PCR and a 3D pellet culture system. In vivo, we assessed cartilage restoration by combining aripiprazole with a scaffold and implanting it into artificially induced cartilage defects in Sprague-Dawley rats. Subsequent mRNA sequencing provided insights into the mechanistic pathways involved. Our results showed that aripiprazole significantly increased mRNA expression of COL2A1 and SOX9, markers of chondrogenesis, and promoted chondrogenic condensation in vitro. Furthermore, aripiprazole effectively enhanced cartilage regeneration in the rat model. KEGG pathway and Gene Ontology Biological Processes (GOBP) analyses of the mRNA sequencing data revealed that aripiprazole upregulated genes related to ribosomes and cytoplasmic translation, thereby facilitating chondrogenesis. In conclusion, our findings suggest that aripiprazole is a promising candidate for improving damaged cartilage, offering a novel approach to cartilage regeneration.
关节软骨的再生能力有限，导致受损组织的自发愈合能力较差。尽管为促进软骨修复进行了各种科学努力，但没有一种单一方法取得了令人满意的结果。随着药物开发成本的不断上升，药物重新定位已成为一种可行的替代方案。本研究旨在通过分析来自基因表达综合数据库（GEO）的与软骨形成相关的微阵列数据，确定一种能够改善软骨缺损的药物。我们利用数据集GSE69110、GSE107649、GSE111822和GSE116173来鉴定与软骨分化相关的基因，使用StringTie进行差异基因表达分析，并从药物-基因相互作用数据库中提取药物数据。此外，我们旨在通过细胞和动物模型实验来验证所鉴定药物的软骨再生潜力。我们使用qRT-PCR和三维微球培养系统评估了阿立哌唑对脂肪来源间充质干细胞（ADMSCs）和软骨细胞的影响。在体内，我们将阿立哌唑与支架结合并植入Sprague-Dawley大鼠的人工诱导软骨缺损中，评估软骨修复情况。随后的mRNA测序提供了对所涉及的机制途径的见解。我们的结果表明，阿立哌唑显著增加了软骨形成标志物COL2A1和SOX9的mRNA表达，并在体外促进了软骨形成聚集。此外，阿立哌唑在大鼠模型中有效地增强了软骨再生。对mRNA测序数据的KEGG通路和基因本体生物学过程（GOBP）分析表明，阿立哌唑上调了与核糖体和细胞质翻译相关的基因，从而促进软骨形成。总之，我们的研究结果表明，阿立哌唑是改善受损软骨的一个有前景的候选药物，为软骨再生提供了一种新方法。
