1. miR-708-5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway.
- Author
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Xu L, Zhang Y, Yu J, Huo W, Xu J, Yang H, Zhang M, Yu S, Wu Y, and Wang M
- Subjects
- Animals, Female, Mice, Rats, Cartilage, Articular metabolism, Cartilage, Articular pathology, Cellular Senescence genetics, Mice, Inbred C57BL, Osteoarthritis genetics, Osteoarthritis metabolism, Osteoarthritis pathology, Rats, Sprague-Dawley, Signal Transduction, Temporomandibular Joint pathology, Temporomandibular Joint metabolism, Chondrocytes metabolism, Mandibular Condyle pathology, MicroRNAs genetics, NF-kappa B metabolism, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism
- Abstract
Objective: Ageing and aberrant biomechanical stimulation are two major risk factors for osteoarthritis (OA). One of the main characteristics of aged cartilage is cellular senescence. One of the main characteristics of osteoarthritic joints is cartilage degeneration. The cells in the temporomandibular joint (TMJ) cartilage are zonally arranged. The deep zone cells are differentiated from the superficial zone cells (SZCs). The purpose of the present study was to investigate whether degenerative shear stress (SS) stimulates the senescence programme in TMJ SZCs, and to determine which miRNA is involved in this process., Method: SZCs were isolated from the TMJ condyles of 3-week-old rats and treated with continuous passaging or SS. RNA sequencing was conducted to identify miRNA(s) that overlap with those involved in the replication senescence process and the SS-induced degeneration programme. Unilateral anterior crossbite (UAC), which is TMJ-OA inducible, was applied to 2-month-old and 12-month-old mice for 3 weeks. The effect of TMJ local injection of agomiR-708-5p was evaluated histologically., Results: Both replication and SS treatment induced SZC senescence. miR-708-5p was identified. Knocking down miR-708-5p in SS-treated SZCs led to more severe senescence by alleviating the inhibitory impact of miR-708-5p on the TLR4/NF-κB pathway. miR-708-5p expression in mouse TMJ cartilage decreased with age. UAC induced more severe osteoarthritic cartilage lesions in 12-month-old mice than in 2-month-old mice. Injection of agomiR-708-5p suppressed UAC-induced osteoarthritic cartilage lesions., Conclusions: Age-related miR-708-5p deficiency is involved in the mechanically stimulated OA process. Intra-articular administration of agomiR-708-5p is a promising new strategy for OA treatment., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
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