PDF(Pubmed)
Abstract：
OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. β-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of β-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism.
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.
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.
摘要：
目的：颞下颌关节骨关节炎(TMJOA)是一种以细胞外基质变性和髁突软骨炎症反应为特征的慢性退行性关节疾病。β-arrestin2是炎症反应的重要调节因子,虽然它在TMJOA中的作用仍然未知。本研究的目的是探讨β-arrestin2在TMJOA早期发展中的作用及其机制。
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。
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。
