Qiao Jie, Cheng Chang, Yang Gongxu, Zhong Chuanqi, Jin Jun, Wu Bin
Department of Orthopedics, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China.
Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, China.
Curr Pharm Biotechnol. 2024 Oct 7. doi: 10.2174/0113892010316076240924072658.
This study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation.
Chondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis- related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated.
JGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses.
Our findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.
本研究旨在探讨健骨方（JGR）对叔丁基过氧化氢（TBHP）诱导的氧化应激下软骨细胞反应的影响，特别关注细胞凋亡和细胞外基质（ECM）降解。
用不同浓度的JGR处理软骨细胞，并评估细胞活力。评估JGR对TBHP诱导的细胞凋亡以及凋亡相关分子（Bcl-2、Bax和裂解的caspase-3）和ECM成分（胶原蛋白II、聚集蛋白聚糖、基质金属蛋白酶-13）蛋白表达水平的影响。
JGR对软骨细胞的氧化应激具有保护作用。此外，它在叔丁基过氧化氢（TBHP）诱导下维持细胞活力，抑制凋亡（Bax、裂解的caspase-3）并增强抗凋亡的Bcl-2。JGR还减轻了细胞外基质（ECM）降解，促进胶原蛋白II和聚集蛋白聚糖，同时降低基质金属蛋白酶-13的表达。研究内质网（ER）应激发现，JGR下调TBHP诱导的GRP78、CHOP、ATF4、p-PERK和p-eIF2α，从而表明对ER应激的调节作用。沉默信息调节因子1（SIRT1）起关键作用，因为JGR上调SIRT1，减轻TBHP诱导的下调。SIRT1基因敲低逆转了JGR的保护作用，突出了其在JGR介导的反应中的关键作用。
我们的研究结果表明，JGR减轻了TBHP诱导的软骨细胞凋亡和ECM降解，突出了其在骨关节炎中的潜在治疗应用。从机制上讲，我们的研究强调SIRT1在介导JGR对ER应激诱导的软骨细胞凋亡和ECM降解的保护作用中起关键作用，为进一步临床探索治疗骨关节炎提供了基础。
