Single-cell RNA sequencing reveals neurovascular-osteochondral network crosstalk during temporomandibular joint osteoarthritis: Pilot study in a human condylar cartilage

PURPOSE: Temporomandibular joint osteoarthritis (TMJ-OA) is one of the most complex temporomandibular disorders, causing pain and dysfunction. The main pathological feature of TMJ-OA is neurovascular invasion from the subchondral bone to the condylar cartilage. This study aimed to discover the cells and genes that play an important role in the neurovascular–osteochondral network crosstalk in human TMJ-OA. MATERIALS AND METHODS: Condylar cartilages from patient with TMJ-OA were divided into OA group, and others from patients with benign condylar hyperplasia (CH) were used as control for further single-cell RNA-sequencing (scRNA-seq). Hematoxylin and eosin staining were performed. The cells and genes in the condylar cartilage were identified and analyzed by scRNA-seq. RESULTS: Histological analysis revealed blood vessel invasion and ossification in the TMJ-OA condylar cartilage. The scRNA-seq identified immune cells, endothelial cells, and chondrocytes in the TMJ-OA condylar cartilage. Macrophages, especially M1-like macrophages, contributed to the inflammation, angiogenesis, and innervation. CD31(+) endothelial cells contributed to the bone mineralization. The TMJ-OA cartilage chondrocytes highly expressed genes related to inflammation, angiogenesis, innervation, and ossification. The hub genes contributing to these processes in the TMJ-OA chondrocytes included CTGF, FBN1, FN1, EGFR, and ITGA5. CONCLUSION: Our study marks the first time scRNA-seq was used to identify the cells and genes in a human TMJ-OA condylar cartilage, and neurovascular–osteochondral network crosstalk during the human TMJ-OA process was demonstrated. Targeting the crosstalk of these processes may be a potential comprehensive and effective therapeutic strategy for human TMJ-OA.