Defining subcellular synovial responses in TMJ osteoarthritis onset via mechanical stress and articular disk derangement models

Kazuhiro Shibusaka; Soichiro Negishi; Asuka Terashima; Miki Maemura; Hiroshi Yoshida; Masahiro Hosonuma; Nobuhiro Sakai; Young Kwan Kim; Yutaka Suzuki; Hiroyuki Okada; Fumiko Yano

doi:10.1038/s41368-025-00411-6

International Journal of Oral Science ›› 2026, Vol. 18 ›› Issue (1) :28 DOI: 10.1038/s41368-025-00411-6

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Defining subcellular synovial responses in TMJ osteoarthritis onset via mechanical stress and articular disk derangement models

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¹Department of Biochemistry, Graduate School of Dentistry, Showa Medical University, Shinagawa-ku, Tokyo, Japan

²Department of Orthodontics, Graduate School of Dentistry, Showa Medical University, Ota-ku, Tokyo, Japan

³Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Showa Medical University, Ota-ku, Tokyo, Japan

⁴Bone and Cartilage Regenerative Medicine, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan

⁵Department of Pharmacology, Graduate School of Pharmacy, Showa Medical University, ai, Shinagawa-ku, Tokyo, Japan

⁶Division of Dental Education, School of Dentistry, Showa Medical University, Shinagawa-ku, Tokyo, Japan

⁷Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan

⁸Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa-shi, Chiba, Japan

⁹Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

¹⁰Showa Medical University Research Administration Center, Showa Medical University, Shinagawa-ku, Tokyo, Japan

^a fumikoyano@dent.showa-u.ac.jp

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Abstract

Temporomandibular joint osteoarthritis (TMJ-OA), the most common degenerative disease of the TMJ, is influenced by various adaptive, inflammatory, and mechanical stressors. In this study, we describe molecular alterations of the synovium of the articular disk in response to mechanical and inflammatory stimuli. Using an integrated transcriptomic approach combining subcellular spatial transcriptomics and single-cell RNA sequencing in murine models of mechanical stress and articular disk derangement, we characterized synovial changes associated with adipogenesis, fibrosis, and macrophage activation. In addition, cell type–and cluster–specific catabolic changes were observed under these stress conditions, suggesting potential contributions to TMJ-OA onset. These results provide a methodology-oriented resource for investigating the molecular pathology of TMJ disorders and may help guide future studies toward the development of targeted therapeutic strategies.

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Kazuhiro Shibusaka, Soichiro Negishi, Asuka Terashima, Miki Maemura, Hiroshi Yoshida, Masahiro Hosonuma, Nobuhiro Sakai, Young Kwan Kim, Yutaka Suzuki, Hiroyuki Okada, Fumiko Yano. Defining subcellular synovial responses in TMJ osteoarthritis onset via mechanical stress and articular disk derangement models. International Journal of Oral Science, 2026, 18(1): 28 DOI:10.1038/s41368-025-00411-6

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