急性加载对晚期膝骨关节炎患者关节软骨基因表达和糖胺聚糖组成的影响较小：一项随机对照试验。

Acute loading has minor influence on human articular cartilage gene expression and glycosaminoglycan composition in late-stage knee osteoarthritis: a randomised controlled trial.

机构信息

Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M81, Copenhagen University Hospital of Bispebjerg and Frederiksberg, Copenhagen, Denmark; Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Osteoarthritis Cartilage. 2023 Jul;31(7):884-893. doi: 10.1016/j.joca.2023.01.317. Epub 2023 Jan 30.

DOI:10.1016/j.joca.2023.01.317

PMID:36720425

Abstract

OBJECTIVE

Osteoarthritis (OA) remains clinically challenging. Regular physical exercise improves symptoms though it is unclear whether exercise influences cartilage at the molecular level. Thus, we aimed to determine the effect of acute loading on gene expression and glycosaminoglycan (GAG) content in human OA cartilage.

DESIGN

Patients with primary knee OA participated in this single-blind randomised controlled trial initiated 3.5 h prior to scheduled joint replacement surgery with or without loading by performing one bout of resistance exercise (one-legged leg press). Cartilage from the medial tibia condyle was sampled centrally, under the meniscus, and from peripheral osteophytes. Samples were analysed for gene expression by real-time reverse transcriptase polymerase chain reaction, and hyaluronidase-extracted matrix was analysed for GAG composition by immuno- and dimethyl-methylene blue assays.

RESULTS

Of 32 patients randomised, 31 completed the intervention: mean age 69 ± 7.5 years (SD), 58% female, BMI 29.4 ± 4.4 kg/m. Exercise increased chondroitin sulphate extractability [95% CI: 1.01 to 2.46; P = 0.0486] but cartilage relevant gene expression was unchanged. Regionally, the submeniscal area showed higher MMP-3, MMP-13, IGF-1Ea, and CTGF, together with lower lubricin and COMP expression compared to the central condylar region. Further, osteophyte expression of MMP-1, MMP-13, IGF-1Ea, and TGF-β3 was higher than articular cartilage and lower for aggrecan, COMP, and FGF-2. Hyaluronidase-extracted matrix from central condylar cartilage contained more GAGs but less chondroitin sulphate compared to submeniscal cartilage.

CONCLUSION

Acute exercise had minor influence on cartilage GAG dynamics, indicating that osteoarthritic cartilage is not significantly affected by acute exercise. However, the regional differences suggest a chronic mechanical influence on human cartilage.

GOV REGISTRATION NUMBER

NCT03410745.

摘要

目的

骨关节炎（OA）仍然具有临床挑战性。定期进行体育锻炼可以改善症状，但尚不清楚锻炼是否会对软骨的分子水平产生影响。因此，我们旨在确定急性负荷对人 OA 软骨基因表达和糖胺聚糖（GAG）含量的影响。

设计

患有原发性膝骨关节炎的患者参与了这项单盲随机对照试验，该试验在计划的关节置换手术前 3.5 小时开始，患者进行了一次抗阻运动（单腿腿压）以进行负荷或不进行负荷。从内侧胫骨髁的半月板下中央、半月板下和骨赘处采集软骨样本。通过实时逆转录聚合酶链反应分析基因表达，通过透明质酸酶提取基质，并通过免疫和二甲亚甲基蓝测定分析 GAG 组成。

结果

32 名随机患者中，31 名完成了干预：平均年龄 69 ± 7.5 岁（标准差），58%为女性，BMI 29.4 ± 4.4kg/m。运动增加了软骨素硫酸盐的可提取性[95%置信区间：1.01 至 2.46；P=0.0486]，但软骨相关基因表达没有变化。区域上，半月板下区域的 MMP-3、MMP-13、IGF-1Ea 和 CTGF 表达较高，而滑液素和 COMP 表达较低，与中央髁间区相比。此外，骨赘处的 MMP-1、MMP-13、IGF-1Ea 和 TGF-β3 表达高于关节软骨，而聚集蛋白聚糖、COMP 和 FGF-2 表达低于关节软骨。来自中央髁间软骨的透明质酸酶提取基质含有更多的 GAGs，但软骨素硫酸盐含量低于半月板下软骨。