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骨关节炎小鼠中曲马多负调控软骨下骨的微观结构和力学性能。

Microstructure and mechanical properties of subchondral bone are negatively regulated by tramadol in osteoarthritis in mice.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China.

Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, Jiangsu, P.R. China.

出版信息

Biosci Rep. 2020 Sep 30;40(9). doi: 10.1042/BSR20194207.

Abstract

OBJECTIVES

In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties.

METHODS

A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention.

RESULTS

In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not.

CONCLUSION

Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.

摘要

目的

在骨关节炎(OA)的治疗中,曲马多作为一种常用的弱阿片类药物,因其对疼痛的抑制作用而受到关注。本研究旨在探讨曲马多对软骨下骨的影响,特别是对其微观结构和力学性能的改变。

方法

本研究通过内侧半月板不稳定(DMM)建立了 OA 小鼠模型。给予载体或药物治疗 4 周。通过微计算机断层扫描(micro-CT)、扫描电子显微镜(SEM)、原子力显微镜(AFM)和组织学染色对不同干预方式的小鼠膝关节进行放射学和组织学分析,评估标本。

结果

在 DMM 诱导的 OA 早期,OA 组的软骨下骨体积分数明显高于 sham+vehicle(sham+veh)组,而治疗组的体积分数低于 DMM+vehicle(DMM+veh)和 sham+veh 组。此外,治疗组的弹性模量明显低于 DMM+veh 和 sham+veh 组。SEM 观察软骨下骨表面显示出严重的破坏,主要表现为陷窝减少和更多且更分散的裂纹。组织学染色表明,无论是否使用曲马多,关节软骨或滑膜细胞的退变均无差异。

结论

尽管曲马多在早期 OA 中有效抑制疼痛,但它会负调节关节软骨下骨的微观结构和力学性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0d/7475645/b3d39f02dcb1/bsr-40-bsr20194207-g1.jpg

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