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建立一种炎症上调的小鼠髌腱病退行性变模型。

Establishment of a Mouse Degenerative Model of Patellar Tendinopathy with Upregulation of Inflammation.

机构信息

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.

出版信息

Int J Mol Sci. 2024 Mar 29;25(7):3847. doi: 10.3390/ijms25073847.

Abstract

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young's modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.

摘要

目前尚无髌腱病的小鼠模型。本研究旨在建立一种小鼠炎症性和退行性髌腱损伤模型,这将有助于使用包括转基因模型在内的先进分子工具研究髌腱病。在不同剂量(低剂量(LD)、中剂量(MD)、高剂量(HD))的胶原酶或生理盐水注入小鼠髌腱。在注射后第 1、2、4 和 8 周,采集肌腱进行组织学检查,并在第 8 周通过微计算机断层扫描(microCT)成像进一步检查。最优剂量组和生理盐水组通过免疫组织化学染色、步态模式和生物力学特性进行进一步评估。胶原酶注射后,组织病理学评分呈剂量依赖性增加。观察到异位矿化,并随胶原酶剂量增加而增加。选择 LD 组进行进一步分析。注射后,IL-10、TNF-α 和 MMP-1 的表达显著增加。与损伤前状态相比,肢体闲置指数(ΔLII)的变化明显更高,而 LD 组的最终载荷、刚度、最终应力和最大杨氏模量明显低于生理盐水组。通过组织病理学、异位钙化、生物力学特性和与疼痛相关的步态变化的剂量依赖性增加,建立了一种类似于腱病的小鼠炎症退行性髌腱损伤模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75e0/11011606/03f704e1aec7/ijms-25-03847-g001.jpg

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