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.
Osteoarthritis Cartilage. 2024 Jun;32(6):666-679. doi: 10.1016/j.joca.2024.02.007. Epub 2024 Feb 23.
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.
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.
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.
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.
衰老和异常的生物力学刺激是骨关节炎（OA）的两个主要危险因素。老年软骨的主要特征之一是细胞衰老。骨关节炎关节的主要特征之一是软骨退化。颞下颌关节（TMJ）软骨中的细胞呈带状排列。深层区细胞从浅层区细胞（SZC）分化而来。本研究旨在探讨退行性剪应力（SS）是否刺激 TMJ SZC 的衰老程序，并确定在此过程中涉及哪些 miRNA。
从 3 周龄大鼠 TMJ 髁突中分离 SZC，并进行连续传代或 SS 处理。进行 RNA 测序以鉴定与复制衰老过程和 SS 诱导的退变程序重叠的 miRNA(s)。将单侧前牙交叉咬合（UAC）应用于 2 月龄和 12 月龄小鼠 3 周，以诱导 TMJ-OA。评估 TMJ 局部注射 agomiR-708-5p 的效果。
复制和 SS 处理均诱导 SZC 衰老。鉴定出 miR-708-5p。在 SS 处理的 SZC 中敲低 miR-708-5p 可通过减轻 miR-708-5p 对 TLR4/NF-κB 通路的抑制作用导致更严重的衰老。随着年龄的增长，miR-708-5p 在小鼠 TMJ 软骨中的表达减少。UAC 在 12 月龄小鼠中引起的骨关节炎性软骨病变比 2 月龄小鼠更严重。注射 agomiR-708-5p 抑制了 UAC 诱导的骨关节炎性软骨病变。
与年龄相关的 miR-708-5p 缺乏参与了机械刺激性 OA 过程。关节内给予 agomiR-708-5p 是治疗 OA 的一种有前途的新策略。
