Relationship between autophagy and NLRP3 inflammasome during articular cartilage degradation in oestrogen-deficient rats with streptozotocin-induced diabetes

IF 2 3区 医学 Q2 ANATOMY & MORPHOLOGY
Rinaldo Florencio-Silva , Gisela Rodrigues da Silva Sasso , Estela Sasso-Cerri , Paulo Sérgio Cerri , Cristiane Damas Gil , Manuel de Jesus Simões
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引用次数: 0

Abstract

Background

Estrogen deficiency and Diabetes mellitus (DM) cause joint tissue deterioration, although the mechanisms are uncertain. This study evaluated the immunoexpression of autophagy and NLRP3-inflammasome markers, in rat articular cartilage with estrogen deficiency and DM.

Methods

Twenty rats were sham-operated (SHAM) or ovariectomized (OVX) and equally allocated into four groups: SHAM and OVX groups administered with vehicle solution; SHAM and OVX groups treated with 60 mg/kg/body weight of streptozotocin, intraperitoneally, to induce DM (SHAM-DM and OVX-DM groups). After seven weeks, the rats were euthanized, and their joint knees were processed for paraffin embedding. Sections were stained with haematoxylin-eosin, toluidine blue, safranin-O/fast-green or subjected to picrosirius-red-polarisation method; immunohistochemistry to detect beclin-1 and microtubule-associated protein 1B-light chain 3 (autophagy markers), NLRP3 and interleukin-1β (IL-1β) (inflammasome activation markers), along with matrix metalloproteinase-9 (MMP-9), Nuclear factor-kappa B (NFκB), and Vascular endothelial growth factor A (VEGF-A) were performed.

Results

Deterioration of articular cartilage and subchondral bone were greater in SHAM-DM and OVX-DM groups. Higher percentages of immunolabeled chondrocytes to NLRP3, IL-1β, MMP-9, NFκB, and VEGF-A, as well as lower percentages of chondrocytes immunolabeled to autophagy markers, were noticed in estrogen-deficient and diabetic groups. These differences were greater in the OVX-DM group. Percentages of immunolabeled chondrocytes showed negative correlation between autophagy markers v.s IL-1β, NLRP-3, MMP-9, NFκB, and VEGF-A, along with positive correlation between VEGF-A vs. MMP-9, NFκB, IL-1β, and NLRP3, and MMP-9 vs. NFκB.

Conclusions

In conclusion, autophagy reduction and NLRP3 inflammasome activation in chondrocytes may be implicated in articular cartilage degradation, under estrogen-deficient and DM conditions. Moreover, the combination of estrogen deficiency and DM may potentiate those effects.

链脲佐菌素诱发糖尿病的雌激素缺乏大鼠关节软骨降解过程中自噬与 NLRP3 炎性体之间的关系
背景:雌激素缺乏和糖尿病(DM)会导致关节组织恶化,但其机制尚不明确。本研究评估了雌激素缺乏和糖尿病大鼠关节软骨中自噬和NLRP3-炎症标志物的免疫表达:20只大鼠分别接受假手术(SHAM)或卵巢切除术(OVX),平均分为4组:SHAM组和OVX组使用载体溶液;SHAM组和OVX组腹腔注射60毫克/千克/体重的链脲佐菌素诱导DM(SHAM-DM组和OVX-DM组)。七周后,对大鼠实施安乐死,并对其膝关节进行石蜡包埋处理。切片用血红素-伊红、甲苯胺蓝、安全素-O/快绿染色,或用皮色素-红-极化法染色;免疫组化检测自噬标记物beclin-1和微管相关蛋白1B-轻链3、炎性小体激活标记物NLRP3和白细胞介素-1β、基质金属蛋白酶-9、核因子卡巴B和血管内皮生长因子A。结果显示SHAM-DM组和OVX-DM组的关节软骨和软骨下骨恶化程度更大。雌激素缺乏组和糖尿病组软骨细胞免疫标记NLRP3、IL-1β、MMP-9、NFκB和VEGF-A的百分比较高,免疫标记自噬标记物的软骨细胞百分比较低。这些差异在OVX-DM组中更大。免疫标记软骨细胞的百分比显示,自噬标记与IL-1β、NLRP-3、MMP-9、NFκB和VEGF-A呈负相关,VEGF-A与MMP-9、NFκB、IL-1β和NLRP3呈正相关,MMP-9与NFκB呈正相关:总之,在雌激素缺乏和DM条件下,软骨细胞中的自噬减少和NLRP3炎性体激活可能与关节软骨降解有关。此外,雌激素缺乏和 DM 的结合可能会增强这些效应。
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来源期刊
Annals of Anatomy-Anatomischer Anzeiger
Annals of Anatomy-Anatomischer Anzeiger 医学-解剖学与形态学
CiteScore
4.40
自引率
22.70%
发文量
137
审稿时长
33 days
期刊介绍: Annals of Anatomy publish peer reviewed original articles as well as brief review articles. The journal is open to original papers covering a link between anatomy and areas such as •molecular biology, •cell biology •reproductive biology •immunobiology •developmental biology, neurobiology •embryology as well as •neuroanatomy •neuroimmunology •clinical anatomy •comparative anatomy •modern imaging techniques •evolution, and especially also •aging
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