血管紧张素 II 引发实验性骨关节炎的膝关节损伤。

Angiotensin II triggers knee joint lesions in experimental osteoarthritis.

机构信息

Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

Department of Metallurgical Engineering and Materials, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

Bone. 2021 Apr;145:115842. doi: 10.1016/j.bone.2021.115842. Epub 2021 Jan 7.

DOI:10.1016/j.bone.2021.115842

PMID:33422700

Abstract

OBJECTIVES

This study aimed to evaluate the involvement of Angiotensin II (Ang II) in joint lesions associated with osteoarthritis (OA) in vitro and in vivo.

METHODS

Chondrocyte cultures were obtained from knee joints of neonatal rats and stimulated with Ang II/MIA/ACE inhibitors. In vivo, rats treated or not with the ACE inhibitor captopril, received daily injections of Ang II or sodium monoiodoacetate (MIA) in knee joints for evaluation of cartilage, bone, and synovial lesions.

RESULTS

Cultured chondrocytes expressed the mRNA for Ace, Agtr1, Agtr2, and Mas1. Stimulating cells with Ang II reduced chondrocyte viability and metabolism. Accordingly, in vivo Ang II injection into the knees of rats triggered hyperalgesia, joint edema, increased the number of leukocytes in the joint cavity, and induced cartilage lesions associated with OA alterations. In further experiments, Ang II synthesis was prevented with the ACE inhibitor Captopril in the context of MIA-induced OA. Ang II inhibition with captopril improved the OARSI score, induced chondroprotection, and reduced the leukocyte recruitment from synovium after MIA. Additionally, captopril prevented MIA-induced bone resorption, by decreasing the number of osteoclasts and increasing the expression of IL-10 in the bone. In vitro, inhibiting Ang II synthesis decreased MIA-induced chondrocyte death and increased Col2a1 transcription.

CONCLUSION

Ang II induces chondrocyte death and joint tissue damages associated with OA and its modulation can be a therapeutic strategy in osteoarthritis.

摘要

目的

本研究旨在评估血管紧张素 II（Ang II）在体外和体内与骨关节炎（OA）相关的关节病变中的作用。

方法

从新生大鼠膝关节中获取软骨细胞，并使用 Ang II/MIA/ACE 抑制剂进行刺激。在体内，用 ACE 抑制剂卡托普利处理或不处理的大鼠，每日在膝关节内注射 Ang II 或单碘乙酸钠（MIA），以评估软骨、骨和滑膜病变。

结果

培养的软骨细胞表达 Ace、Agtr1、Agtr2 和 Mas1 的 mRNA。用 Ang II 刺激细胞会降低软骨细胞的活力和代谢。因此，向大鼠膝关节内注射 Ang II 会引发痛觉过敏、关节肿胀、增加关节腔白细胞数量，并诱导与 OA 改变相关的软骨病变。在进一步的实验中，在 MIA 诱导的 OA 中，使用 ACE 抑制剂卡托普利阻止 Ang II 的合成。用卡托普利抑制 Ang II 可改善 OARSI 评分，诱导软骨保护，并减少 MIA 后滑膜白细胞的募集。此外，卡托普利可通过减少破骨细胞数量和增加骨内 IL-10 的表达来预防 MIA 诱导的骨吸收。在体外，抑制 Ang II 的合成可减少 MIA 诱导的软骨细胞死亡并增加 Col2a1 的转录。