Upregulated Mitochondrial Dynamics Is Responsible for the Procatabolic Changes of Chondrocyte Induced by α2-Adrenergic Signal Activation.

IF 2.7 4区医学 Q1 ORTHOPEDICS CARTILAGE Pub Date : 2024-12-01 Epub Date: 2023-08-30 DOI:10.1177/19476035231189841

Jiaying He, Wenpin Qin, Yusong Zhang, Jianfei Yan, Xiaoxiao Han, Jialu Gao, Qihong Li, Kai Jiao

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Abstract

Objective: Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study.

Design: Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated.

Results: We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE.

Conclusions: The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that "α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.

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线粒体活力上调是α2-肾上腺素能信号激活诱导软骨细胞促分解代谢变化的原因。

目的：交感神经张力的激活对骨关节炎（OA）软骨的退化非常重要。最近的研究报告称，交感神经信号可影响靶细胞的线粒体功能。目前还不清楚这种影响是否会在软骨细胞中产生并影响软骨细胞的分解代谢。本研究调查了线粒体动力学在激活α2-肾上腺素能信号介导的软骨细胞分解代谢中的作用：设计：仅用去甲肾上腺素（NE）刺激原代软骨细胞，或用α2-肾上腺素能受体（Adra2）拮抗剂（育亨宾）预处理后再用NE刺激原代软骨细胞。研究了软骨细胞新陈代谢及其线粒体动力学的变化：结果：我们发现 NE 刺激会诱导软骨细胞基质金属蛋白酶-3 基因和蛋白表达的增加以及 aggrecan 水平的降低。与用药物治疗的对照组相比，线粒体生成和线粒体数量均有所上升。线粒体融合和分裂以及有丝分裂吞噬也在 NE 的刺激下显著增加。抑制 Adra2 可减轻 NE 诱导的软骨细胞分解代谢和线粒体动态变化：本研究结果表明，通过线粒体生成、融合、裂变和有丝分裂来上调线粒体动力学是激活α2-肾上腺素能信号介导的软骨细胞分解代谢的原因。α2-肾上腺素能信号激活通过上调软骨细胞线粒体动力学促进颞下颌关节骨关节炎（TMJ-OA）软骨退化 "的假设得到了验证。这表明在 TMJ-OA 的软骨细胞中存在一种新的调控机制，可抑制线粒体融合和分裂的异常激活，是改善线粒体功能和抑制软骨细胞损伤的潜在调控因子，并为预防 TMJ-OA 开创了一个潜在的创新治疗方向。

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来源期刊

CARTILAGE ORTHOPEDICS-

CiteScore

6.90

自引率

7.10%

发文量

期刊介绍： CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair. The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers. The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.