A loss of primary cilia by a reduction in mTOR signaling correlates with age-related deteriorations in condylar cartilage.

IF 5.3 2区 医学 Q1 GERIATRICS & GERONTOLOGY GeroScience Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI:10.1007/s11357-024-01143-x
Megumi Kitami, Masaru Kaku, Lay Thant, Takeyasu Maeda
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Abstract

Age-related deterioration of condylar cartilage is an etiological factor in temporomandibular joint-osteoarthritis (TMJ-OA). However, its underlying mechanism remains unknown. Therefore, we examined age-related changes and the relationship between mTOR signaling and primary cilia in condylar cartilage to determine the intrinsic mechanisms of age-related TMJ-OA. Age-related morphological changes were analyzed using micro-computed tomography and safranin O-stained histological samples of the mandibular condyle of C57BL/6J mice (up to 78 weeks old). Immunohistochemistry was used to assess the activity of mTOR signaling, primary cilia frequency, and Golgi size of condylar chondrocytes. Four-week-old mice receiving an 11-week series of intraperitoneal injections of rapamycin, a potent mTOR signaling inhibitor, were used for the histological evaluation of the condylar cartilage. The condylar cartilage demonstrated an age-related reduction in cartilage area, including chondrocyte size, cell density, and cell size distribution. The Golgi size, primary cilia frequency, and mTOR signaling also decreased with age. Rapamycin injections resulted in both diminished cartilage area and cell size, resembling the phenotypes observed in aged mice. Rapamycin-injected mice also exhibited a smaller Golgi size and lower primary cilia frequency in condylar cartilage. We demonstrated that a loss of primary cilia due to a decline in mTOR signaling was correlated with age-related deteriorations in condylar cartilage. Our findings provide new insights into the tissue homeostasis of condylar cartilage, contributing to understanding the etiology of age-related TMJ-OA.

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mTOR 信号的减少导致初级纤毛的丧失,这与髁状突软骨与年龄相关的退化有关。
与年龄有关的髁状突软骨退化是颞下颌关节骨关节炎(TMJ-OA)的病因之一。然而,其潜在机制仍不清楚。因此,我们研究了髁状突软骨中与年龄相关的变化以及 mTOR 信号传导与初级纤毛之间的关系,以确定与年龄相关的颞下颌关节-骨关节炎的内在机制。我们使用微型计算机断层扫描和C57BL/6J小鼠(78周龄以下)下颌骨髁状突的黄红素O染色组织学样本分析了与年龄相关的形态学变化。免疫组化被用来评估髁状突软骨细胞的 mTOR 信号活性、初级纤毛频率和高尔基体大小。四周大的小鼠腹腔注射雷帕霉素(一种强效的 mTOR 信号抑制剂)11 周后,髁状突软骨的组织学评估就开始了。髁状软骨显示出与年龄相关的软骨面积减少,包括软骨细胞大小、细胞密度和细胞大小分布。高尔基体大小、初级纤毛频率和mTOR信号也随着年龄的增长而减少。注射雷帕霉素会导致软骨面积和细胞体积缩小,这与在老龄小鼠身上观察到的表型相似。注射雷帕霉素的小鼠还表现出较小的高尔基体大小和较低的髁状突软骨初级纤毛频率。我们证明,mTOR 信号转导下降导致的初级纤毛损失与髁状突软骨与年龄相关的退化有关。我们的研究结果为了解髁状突软骨的组织稳态提供了新的视角,有助于理解与年龄相关的颞下颌关节-颌面关节疼痛的病因。
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来源期刊
GeroScience
GeroScience Medicine-Complementary and Alternative Medicine
CiteScore
10.50
自引率
5.40%
发文量
182
期刊介绍: GeroScience is a bi-monthly, international, peer-reviewed journal that publishes articles related to research in the biology of aging and research on biomedical applications that impact aging. The scope of articles to be considered include evolutionary biology, biophysics, genetics, genomics, proteomics, molecular biology, cell biology, biochemistry, endocrinology, immunology, physiology, pharmacology, neuroscience, and psychology.
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