Low-Grade Inflammatory Mediators and Metalloproteinases Yield Synchronous and Delayed Responses to Mechanical Joint Loading.

IF 2.7 4区 医学 Q1 ORTHOPEDICS
CARTILAGE Pub Date : 2024-12-01 Epub Date: 2023-08-24 DOI:10.1177/19476035231193089
Conner W Hutcherson, Michelle Mao, Bhaskar Thakur, Yasin Y Dhaher
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Abstract

Objective: Mechanical loading is an essential factor for the maintenance of joint inflammatory homeostasis and the sensitive catabolic-anabolic signaling cascade involved in maintaining cartilage tissue health. However, abnormal mechanical loading of the joint structural tissues can propagate joint metabolic dysfunction in the form of low-grade inflammation. To date, few studies have attempted to delineate the early cascade responsible for the initiation and perpetuation of stress-mediated inflammation and cartilage breakdown in human joints.

Design: Fifteen healthy human male participants performed a walking paradigm on a cross-tilting treadmill platform. Blood samples were collected before exercise, after 30 minutes of flat walking, after 30 minutes of tilted walking, and after an hour of rest. Serum concentrations of the following biomarkers were measured: interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, transforming growth factor beta (TGF)-β, tissue inhibitor of matrix metalloproteinase 1 (TIMP)-1, and cartilage oligomeric protein (COMP).

Results: Luminex Multiplex analysis of serum showed increased concentrations of COMP, IL-1β, TNF-α, IL-10, and TGF-β from samples collected after flat and cross-tilted treadmill walking compared to baseline. Serum concentrations of MMP-1 and MMP-13 also increased, but primarily in samples collected after tilted walking. Pearson's correlation analysis showed positive correlations between the expression of COMP, TNF-α, IL-10, and MMP-13 at each study timepoint.

Conclusion: Stress-mediated increases in serum COMP during exercise are associated with acute changes in pro and anti-inflammatory molecular activity and subsequent changes in molecules linked to joint tissue remodeling and repair.

低级炎症介质和金属蛋白酶对机械关节加载产生同步和延迟反应。
目的:机械负荷是维持关节炎症平衡和敏感的分解代谢-合成代谢信号级联的重要因素,参与维持软骨组织的健康。然而,关节结构组织的异常机械负荷会以低度炎症的形式传播关节代谢功能障碍。迄今为止,很少有研究试图确定人体关节中由压力介导的炎症和软骨破坏的早期级联:设计:15 名健康男性参与者在交叉倾斜的跑步机平台上进行行走范式。分别在运动前、平走 30 分钟后、倾斜行走 30 分钟后和休息一小时后采集血液样本。测量血清中下列生物标志物的浓度:白细胞介素(IL)-1β、IL-6、IL-10、肿瘤坏死因子α(TNF)-α、基质金属蛋白酶(MMP)-1、MMP-3、MMP-9、MMP-13、转化生长因子β(TGF)-β、基质金属蛋白酶1组织抑制剂(TIMP)-1和软骨低聚蛋白(COMP):结果:对血清进行的 Luminex 多重分析表明,与基线相比,在平地和交叉倾斜跑步机行走后采集的样本中,COMP、IL-1β、TNF-α、IL-10 和 TGF-β 的浓度均有所增加。血清中 MMP-1 和 MMP-13 的浓度也有所增加,但主要是在倾斜行走后采集的样本中。皮尔逊相关分析表明,在每个研究时间点,COMP、TNF-α、IL-10和MMP-13的表达均呈正相关:结论:在运动过程中,应激介导的血清COMP增加与促炎和抗炎分子活性的急性变化以及随后与关节组织重塑和修复相关的分子变化有关。
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来源期刊
CARTILAGE
CARTILAGE ORTHOPEDICS-
CiteScore
6.90
自引率
7.10%
发文量
80
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.
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