Single-cell transcriptional atlas reveals distinct immune-chondrocyte crosstalk mechanisms in temporomandibular joint osteoarthritis induced by different types of occlusal disorder

Kang Wang; Yusi Li; Shuaixi Xiang; Ningyi Shao; Peiqi Wang; Xianrui Yang; Xianglong Han; Qingfeng Li; Hui Xu

doi:10.1038/s41368-025-00424-1

International Journal of Oral Science ›› 2026, Vol. 18 ›› Issue (1) :22 DOI: 10.1038/s41368-025-00424-1

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Single-cell transcriptional atlas reveals distinct immune-chondrocyte crosstalk mechanisms in temporomandibular joint osteoarthritis induced by different types of occlusal disorder

Kang Wang ¹^,²
, Yusi Li ³^,⁴
, Shuaixi Xiang ¹^,⁵
, Ningyi Shao ³^,⁶^,⁷
, Peiqi Wang ¹^,⁵
, Xianrui Yang ⁸
, Xianglong Han ¹^,⁵
, Qingfeng Li ⁹
, Hui Xu ¹^,⁵^,^a

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¹State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China

²Department of Plastic and Burn Surgery, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China

³Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China

⁴, The Islands Healthcare Complex-Macao Medical Center of Peking Union Medical College Hospital, Macau SAR, China

⁵Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China

⁶MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao SAR, China

⁷Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China

⁸Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL, USA

⁹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

^a xhhx@scu.edu.cn

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Abstract

Temporomandibular joint (TMJ) osteoarthritis (OA) is a progressive degenerative disease in which the intricate mechanisms of the condyle cartilage damage are yet to be disclosed. A detailed characterization of cellular composition and signal networks involved in the pathogenesis is in need. This study, for the first time, identified chondrocytes heterogeneity and subchondral immune microenvironments based on single-cell transcriptomes of the mouse mandibular condyle, and provided insights into the cellular and signaling basis of the homeostasis of the condyle and pathogenesis of TMJOA by healthy-to-diseased comparisons. The differentially expressed gene pattern distinguished 8 chondrocyte subsets and 9 immune cell types in the condyle. Close interactions were found between these cell populations, with enhanced communication between chondrocytes and immune cell subsets in the condyles subjected to anterior premature contact (APC) model or unilateral anterior crossbite (UAC) model. The single-cell transcriptomic changes suggested predominant roles of neutrophils in immune-chondrocyte interactions in these occlusal disorder models. Neutrophils-derived TNF-α signaling was inferred to be the most greatly enhanced information flow in the condyle of the APC model, while increased Thbs1-Sdc4 signaling in mediating neutrophils-to-chondrocytes interactions was indicated in the UAC-model condyle, with predominant BSP signaling. Interfering in these signaling by drug administration demonstrated therapeutic potential for the APC- or UAC-induced TMJOA.

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Kang Wang, Yusi Li, Shuaixi Xiang, Ningyi Shao, Peiqi Wang, Xianrui Yang, Xianglong Han, Qingfeng Li, Hui Xu. Single-cell transcriptional atlas reveals distinct immune-chondrocyte crosstalk mechanisms in temporomandibular joint osteoarthritis induced by different types of occlusal disorder. International Journal of Oral Science, 2026, 18(1): 22 DOI:10.1038/s41368-025-00424-1

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