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 inflam-mation, 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.