METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and β-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis.
RESULTS: The loss of β-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1β) factors in condylar cartilage were increased in β-arrestin2 null mice compared with WT mice. Moreover, the loss of β-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA.
CONCLUSIONS: In conclusion, we demonstrated for the first time that β-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, β-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.
方法:在八周龄野生型(WT)和β-arrestin2缺乏症小鼠上建立单侧前牙反咬合(UAC)模型,以模拟TMJOA的进展。苏木精-伊红(HE)染色和显微计算机断层扫描(micro-CT)分析用于组织学和影像学评估。进行免疫组织化学以检测炎症和降解细胞因子的表达,以及自噬相关因素。进行末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)测定以评估软骨细胞凋亡。
结果:在早期TMJOA模型中,β-arrestin2的丢失加重了软骨退变和软骨下骨破坏。此外,在UAC组中,与WT小鼠相比,β-arrestin2缺失小鼠髁突软骨中降解因子(Col-X)和炎症因子(TNF-α和IL-1β)的表达增加。此外,β-arrestin2的缺失促进了TMJOA早期软骨细胞的凋亡和自噬过程。
结论:结论:我们首次证明β-arrestin2在早期TMJOA的发展中起保护作用,可能通过抑制软骨细胞的凋亡和自噬过程。因此,β-arrestin2可能是TMJOA的潜在治疗靶点,为TMJOA的早期治疗提供了新的见解。