Raut Rajnikant Dilip, Choudhury Chumki, Chakraborty Amit Kumar, Singh Harpreet, Mehra Pushkar, Gerstenfeld Louis, Almarza Alejandro, Bais Manish V
bioRxiv. 2025 May 18:2025.05.18.654737. doi: 10.1101/2025.05.18.654737.
Osteoarthritis (OA) is a debilitating joint disease that affects millions of people worldwide, with the temporomandibular joint (TMJ) and knee joint being prominently affected. Despite its prevalence, TMJ-OA remains understudied. This study aimed to investigate the transcriptional signature of the TMJ compared to that of the knee joint and to explore transcriptional differences in the medial and superficial layers of the TMJ-OA.
Six-month-old C57BL/6J mice TMJ and knee samples were collected. Goat TMJ superficial and medial layer cartilage was separated and treated with IL-1β. All samples were subjected to bulk RNA sequencing followed by differential expression and gene set enrichment analysis.
We identified 4,031 protein-coding genes differentially expressed in the TMJ compared to the knee, with significant enrichment of neuronal system genes and lower enrichment of innate immune system genes. Key osteoarthritis biomarkers such as , and were more highly expressed in the TMJ, indicating a higher vulnerability to OA development. IL-1β treatment in goat TMJ chondrocytes mimicked the natural TMJ-OA-like transcriptional changes and immune responses, which are also observed in the rabbit TMJ-OA model. This validated the goat TMJ-OA model. The IL-1β-treated goat TMJ medial cartilage layer was enriched in OA-associated transcription factors (TFs), senescence genes, and epigenetic regulators.
Our study demonstrated the unique transcriptomic signature of the TMJ compared with the knee joint, highlighting its vulnerability to OA and pain. These findings provide valuable insights into the molecular mechanisms of TMJ and offer a resource for potential therapeutic target selection for TMJ-OA treatment.
Significant enrichment of neuronal system genes and lower enrichment of innate immune system genes in temporomandibular joint. Key osteoarthritis biomarkers such as , and have higher expression in temporomandibular joint, indicating a higher vulnerability to osteoarthritis development. Interleukin-1beta treatment in goat temporomandibular joint medial layer cartilage mimics natural temporomandibular joint osteoarthritis-like transcriptional changes and immune responses observed in rabbit temporomandibular joint osteoarthritis model.
骨关节炎（OA）是一种使人衰弱的关节疾病，影响着全球数百万人，颞下颌关节（TMJ）和膝关节受影响尤为显著。尽管其发病率高，但颞下颌关节骨关节炎（TMJ-OA）仍研究不足。本研究旨在调查与膝关节相比颞下颌关节的转录特征，并探索TMJ-OA内侧层和表层的转录差异。
收集6月龄C57BL/6J小鼠的颞下颌关节和膝关节样本。分离山羊颞下颌关节表层和内侧层软骨并用白细胞介素-1β（IL-1β）处理。所有样本均进行批量RNA测序，随后进行差异表达和基因集富集分析。
我们鉴定出与膝关节相比在颞下颌关节中差异表达的4031个蛋白质编码基因，其中神经系统基因显著富集，而固有免疫系统基因富集程度较低。关键骨关节炎生物标志物如 、 和 在颞下颌关节中表达更高，表明其发生骨关节炎的易感性更高。山羊颞下颌关节软骨细胞中的IL-1β处理模拟了自然的TMJ-OA样转录变化和免疫反应，这在兔TMJ-OA模型中也有观察到。这验证了山羊TMJ-OA模型。IL-1β处理的山羊颞下颌关节内侧软骨层富含与OA相关的转录因子（TFs）、衰老基因和表观遗传调节因子。
我们的研究证明了颞下颌关节与膝关节相比独特的转录组特征，突出了其对OA和疼痛的易感性。这些发现为颞下颌关节的分子机制提供了有价值的见解，并为TMJ-OA治疗的潜在治疗靶点选择提供了资源。
颞下颌关节中神经系统基因显著富集，固有免疫系统基因富集程度较低。关键骨关节炎生物标志物如 、 和 在颞下颌关节中表达更高，表明其发生骨关节炎的易感性更高。山羊颞下颌关节内侧层软骨中的白细胞介素-1β处理模拟了在兔颞下颌关节骨关节炎模型中观察到的自然颞下颌关节骨关节炎样转录变化和免疫反应。
