SIRT5 對類風濕性關節炎軟骨細胞凋亡的影響

Abstract

類風濕性關節炎（Rheumatoid arthritis, RA）是一種關節損傷之慢性炎症性疾病，造成嚴重的軟骨組織破壞與軟骨細胞凋亡[1]。Sirtuin 5（SIRT5）作為一種轉譯後修飾蛋白酶，在細胞代謝調控中發揮重要作用[7]。已有研究表示，SIRT5 可減輕 RA 導致的關節損傷[12]，然而，其在 RA 發病機制中的具體作用仍有研究空間。軟骨做為維持關節功能的的重要組織，在此研究探討 SIRT5 在 RA 中對軟骨細胞凋亡的影響。 本研究透過體外實驗探討 SIRT5 在軟骨細胞中的作用，採用 SW1353 軟骨細胞並以氯化鈷 (CoCl₂)誘導缺氧，以模擬 RA 關節的病理環境。此外，透過 SIRT5 過表達技術，評估其對軟骨細胞存活率的影響，並結合組織學分析（包括 H&E 染色與 TUNEL 染色）探討 SIRT5 在軟骨細胞凋亡中的角色。 研究結果表示，在缺氧誘導的 SW1353 軟骨細胞中，SIRT5 過表達可顯著提高細胞存活率。此外，動物實驗結果表示，SIRT5 缺失的 CIA 小鼠關節中，軟骨細胞的凋亡程度增加，並伴隨較嚴重的關節損傷。實驗室先前結果中，SIRT5 可能透過降低ROS減輕 RA 症狀。這些結果支持 SIRT5 在 RA 軟骨中的潛在保護作用，未來可進一步研究其是否透過調控氧化壓力與細胞凋亡，減輕 RA 導致的軟骨損傷。

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint damage, leading to severe cartilage tissue destruction and chondrocyte apoptosis [1]. Sirtuin 5 (SIRT5), a post-translational modification enzyme, plays a critical role in regulating cellular metabolism [7]. Previous studies have suggested that SIRT5 can mitigate joint damage caused by RA [12]; however, its specific role in the pathogenesis of RA remains underexplored. As cartilage is a vital tissue for maintaining joint function, this study investigates the effects of SIRT5 on chondrocyte apoptosis in RA.

This study examines the role of SIRT5 in chondrocytes through in vitro experiments, utilizing SW1353 chondrocytes and inducing hypoxia with cobalt chloride (CoCl₂) to mimic the pathological environment of RA joints. Additionally, SIRT5 overexpression techniques were employed to assess its impact on chondrocyte viability, combined with histological analyses (including H&E staining and TUNEL staining) to explore SIRT5’s role in chondrocyte apoptosis.

The results indicate that in hypoxia-induced SW1353 chondrocytes, SIRT5 overexpression significantly enhances cell viability. Furthermore, animal experiments revealed that in SIRT5-deficient collagen-induced arthritis (CIA) mice, the degree of chondrocyte apoptosis in joints increased, accompanied by more severe joint damage. Previous laboratory findings suggest that SIRT5 may alleviate RA symptoms by reducing reactive oxygen species (ROS). The findings of this study support a potential protective role for SIRT5 in RA cartilage, suggesting that future research could further investigate whether SIRT5 mitigates RA-induced cartilage damage by regulating oxidative stress and apoptosis.