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  3. Pyroptosis of chondrocytes activated by synovial inflammation accelerates TMJ osteoarthritis cartilage degeneration via ROS/NLRP3 signaling

Pyroptosis of chondrocytes activated by synovial inflammation accelerates TMJ osteoarthritis cartilage degeneration via ROS/NLRP3 signaling

  • Int Immunopharmacol. 2023 Aug 23;124(Pt A):110781. doi: 10.1016/j.intimp.2023.110781.
Xin Liu 1,  Yanyan Li 1,  Jie Zhao 1,  Zhihui Hu 1,  Wei Fang 1,  Jin Ke 1,  Wei Li 2,  Xing Long 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; Department of Oral Radiology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China. Electronic address: waylee@whu.edu.cn.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China. Electronic address: longxing@whu.edu.cn.
PMID: 37625369 DOI: 10.1016/j.intimp.2023.110781
Abstract

Objectives: Synovial inflammation and chondrocyte death have been widely acknowledged as key contributors to the pathological progression of temporomandibular joint osteoarthritis (TMJ-OA), a degenerative joint disease currently lacking definitive treatments. This study aims to understand the regulatory role of chondrocyte Pyroptosis in condylar cartilage degradation during TMJ-OA.

Methods: The levels of cytokines, cartilage degeneration markers, and pyroptotic biomarkers in the synovium and synovial fluid of temporomandibular disorders (TMD) patients were examined. The synovitis, cartilage degradation, and chondrocyte Pyroptosis in wild-type and alpha-kinase 1 (ALPK1)-deficient TMJ-OA mice were then compared following monosodium iodoacetate (MIA) induction. Subsequently, we investigated the downstream mechanisms of cytokines- or macrophage supernatants-induced metabolic disorders and Pyroptosis in chondrocytes using primary TMJ chondrocytes and ATDC5 chondrocyte cultures.

Results: We found a positive correlation between pyroptotic biomarkers and cartilage degradation mediators and cytokines in the synovial fluid of TMD patients. MIA-induced TMJ-OA mice demonstrated significant synovitis, cartilage degradation, and chondrocyte Pyroptosis, which were mitigated in ALPK1-deficient TMJ-OA mice, inflammation-restrained mice. Ex-vivo study revealed the contribution of Reactive Oxygen Species (ROS) to inflammation-irritated macrophage supernatants-induced Pyroptosis and metabolic disorders in chondrocytes. Targeting NOD-like receptor protein 3 (NLRP3) alleviated cytokines- or ROS-induced Pyroptosis and metabolic disorders in chondrocytes by inhibiting Caspase-1 activation and interleukin-1β (IL-1β) secretion.

Conclusion: Our findings offer novel insight into the role of synovial inflammation-induced chondrocyte Pyroptosis in promoting cartilage degradation during TMJ-OA via the ROS and NLRP3 signaling pathway.

Keywords

Chondrocytes; NLRP3; Pyroptosis; ROS; Synovial inflammation; TMJ-OA.

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