miR-708-5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway

Lingfeng Xu; Yuejiao Zhang; Jia Yu; Wanqiu Huo; Jiali Xu; Hongxu Yang; Mian Zhang; Shibing Yu; Yaoping Wu; Meiqing Wang

doi:10.1016/j.joca.2024.02.007

miR-708-5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway

Osteoarthritis Cartilage. 2024 Feb 23:S1063-4584(24)00049-9. doi: 10.1016/j.joca.2024.02.007. Online ahead of print.

Authors

Lingfeng Xu¹, Yuejiao Zhang², Jia Yu¹, Wanqiu Huo¹, Jiali Xu¹, Hongxu Yang¹, Mian Zhang¹, Shibing Yu¹, Yaoping Wu³, Meiqing Wang⁴

Affiliations

¹ Department of Oral Anatomy and Physiology and TMD, College of Stomatology, the Fourth Military Medical University. Xi'an, China.
² Department of Oral Anatomy and Physiology and TMD, Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
³ Department of Joint Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, China.
⁴ Department of Oral Anatomy and Physiology and TMD, College of Stomatology, the Fourth Military Medical University. Xi'an, China; Department of Oral Anatomy and Physiology and TMD, Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, China. Electronic address: mqwang@fmmu.edu.cn.

PMID: 38403153
DOI: 10.1016/j.joca.2024.02.007

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.

Keywords: Ageing; Chondrocyte; Mechanical stress; MicroRNA; Osteoarthritis; Temporomandibular joint.