运行x2
西妥因1
锡尔图因
转录因子
下调和上调
细胞生物学
软骨细胞
内分泌学
软骨
内科学
化学
医学
NAD+激酶
生物
生物化学
解剖
基因
酶
作者
Kazuo Yudoh,Shu Somemura,Rie Karasawa
标识
DOI:10.1136/annrheumdis-2023-eular.5541
摘要
Background
Mechanical stress is an important factor affecting bone and cartilage tissue homeostasis in osteoarthritis (OA). We focused on the interaction among mechanical stress, glucose uptake via glucose transporter 1 (Glut1) and the cellular energy sensor sirtuin 1 (SIRT1) in energy metabolism, since it has been recognized that SIRT1, an NAD+-dependent deacetylase, may function as a master regulator of mechanical stress response as well as cellular energy metabolism Also, it has already been demonstrated that SIRT1 regulates the activity of the osteogenic transcription factor, runt-related transcription factor 2 (Runx2). Objectives
Purpose of this study was to determine whether mechanical force affects the expression of factors regulating energy metabolism and transcription factors controlling subchondral bone formation and ossification in OA. Methods
Comparative analyses of the expression of Glut1, SIRT1 and Runx2 in osteoblasts and chondrocytes were performed after mechanical loading of a 3D cell–collagen sponge construct. Results
Mechanical loading increased osteoblast activity. Mechanical loading significantly increased the expression of Glut1, significantly decreased the expression of SIRT1 and increased the expression of Runx2 in osteoblasts in comparison with non-loaded osteoblasts. Incubation with Glut1 inhibitor blocked mechanical stress-induced changes in SIRT1 and Runx2 in osteoblasts. In contrast to osteoblasts, expressions of Glut1, SIRT1 and Runx2 in chondrocytes were decreased by loading. Over loading reduced chondrocyte activity (production of proteoglycan, type II collagen). Conclusion
Our present study indicated that mechanical stress induced upregulation of Glut1, downregulation of SIRT1, and upregulation of Runx2 in osteoblasts, but not in chondrocytes. Since SIRT1 is known to negatively regulate Runx2 activity, mechanical stress-induced downregulation of SIRT1 may lead to upregulation of Runx2, resulting in osteoblast differentiation and bone formation. Incubation with Glut1 inhibitor blocked mechanical stress-induced changes in SIRT1 and Runx2 suggesting that Glut1 is necessary to mediate the responses of SIRT1 and Runx2 to mechanical loading. These results suggest that Glut1 regulates mechanical stress-activated subchondral bone formation and ossification via the signal transduction network of cellular energy sensors, sirtuin 1 and Runx2, in OA. REFERENCES:
NIL. Acknowledgements:
NIL. Disclosure of Interests
None Declared.
科研通智能强力驱动
Strongly Powered by AbleSci AI