Bulk RNA-seq analyses of mandibular condylar cartilage in a post-traumatic TMJ osteoarthritis rabbit model.
Bulk RNA-seq analyses of mandibular condylar cartilage in a post-traumatic TMJ osteoarthritis rabbit model.
复制标题
对创伤后颞下颌关节骨关节炎兔模型中的下颌髁软骨进行批量 RNA 测序分析。
DOI：
10.1111/ocr.12649
复制
发表时间：
2023
影响因子：
3.1
通讯作者：
Embree,MildredC
中科院分区：
文献类型：
--
作者：
Tosa,Ikue;Ruscitto,Angela;Wang,Ziyi;Chen,KiraZ;Ono,Mitsuaki;Embree,MildredC
目的颞下颌关节（TMJ）在解剖学上由下颌髁突软骨（CC）和纤维软骨浅表带组成，是进食和咬合的关键部位。TMJ骨关节炎（OA）导致疼痛，关节功能障碍和软骨组织的永久性损失。然而，临床上还没有药物可以改善骨关节炎，而且对导致TMJ骨关节炎的基因的整体概况知之甚少。此外，概括OA发病机制的信号通路复杂性的动物模型对于设计阻止OA进展的新型生物制剂至关重要。我们之前开发了一个新西兰大白兔TMJ损伤模型，显示CC变性。在这里，我们进行了全基因组分析，以确定在OA病理过程中对细胞功能至关重要的新信号通路。材料与方法采用手术诱导新西兰大白兔颌下关节骨性关节炎。损伤后3个月，我们进行了TMJ髁的整体基因表达谱分析。对颞下颌关节髁的RNA样本进行测序。将原始RNA - seq数据映射到相关基因组后，用DESeq2分析差异表达。进行了基因本体富集分析和京都基因与基因组百科全书通路分析。结果/结论sour研究揭示了TMJ OA诱导过程中多种通路的改变，包括Wnt、Notch和PI3K‐Akt信号通路。我们展示了一个动物模型，该模型概括了TMJ OA发病机制的线索和信号的复杂性，这对于开发和测试治疗OA的新型药物至关重要。
ObjectiveThe temporomandibular joint (TMJ) is anatomically comprised of the mandibular condylar cartilage (CC) lined with fibrocartilaginous superficial zone and is crucial for eating and dental occlusion. TMJ osteoarthritis (OA) leads to pain, joint dysfunction and permanent loss of cartilage tissue. However, there are no drugs clinically available that ameliorate OA and little is known about global profiles of genes that contribute to TMJ OA. Furthermore, animal models that recapitulate the complexity of signalling pathways contributing to OA pathogenesis are crucial for designing novel biologics that thwart OA progression. We have previously developed a New Zealand white rabbit TMJ injury model that demonstrates CC degeneration. Here, we performed genome‐wide profiling to identify new signalling pathways critical for cellular functions during OA pathology.Materials and MethodsTemporomandibular joint OA was surgically induced in New Zealand white rabbits. Three months following injury, we performed global gene expression profiling of the TMJ condyle. RNA samples from TMJ condyles were subjected to sequencing. After raw RNA‐seq data were mapped to relevant genomes, differential expression was analysed with DESeq2. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted.Results/ConclusionsOur study revealed multiple pathways altered during TMJ OA induction including the Wnt, Notch and PI3K‐Akt signalling pathways. We demonstrate an animal model that recapitulates the complexity of the cues and signals underlying TMJ OA pathogenesis, which is essential for developing and testing novel pharmacologic agents to treat OA.