PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway.
PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway.
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PARK7 通过调节 Nrf2 信号通路增强骨髓间充质干细胞对应激诱导的细胞凋亡的抵抗力，从而促进早期类固醇诱导的股骨头坏死的修复
DOI：
10.1038/s41419-021-04226-1
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发表时间：
2021-10-13
影响因子：
9
通讯作者：
Dong W
中科院分区：
文献类型：
--
作者：
Zhang F;Yan Y;Peng W;Wang L;Wang T;Xie Z;Luo H;Zhang J;Dong W
骨科迫切需要治疗早期类固醇引起的股骨头坏死（SONFH）的新疗法。骨髓间充质干细胞（BMSC）移植为早期治疗这种疾病提供了新策略。然而，应激诱导的骨髓间充质干细胞移植到股骨头坏死区后会发生细胞凋亡，限制了骨髓间充质干细胞移植的疗效。抑制 BMSC 凋亡是提高该过程功效的关键。在我们之前的研究中，我们证实帕金森病蛋白7（PARK7）在抗氧化防御中具有活性，可以清除活性氧（ROS），保护线粒体，并赋予BMSCs抵抗应激诱导的细胞凋亡的能力。在本研究中，我们研究了驱动 BMSC 中 PARK7 介导的细胞凋亡抵抗的机制。我们的结果表明，PARK7 促进核因子（红细胞衍生 2）样 2 (Nrf2)/Kelch 样松果菊苷相关蛋白 1 (Keap1) 复合物的解体。然后游离的Nrf2进入细胞核，激活锰超氧化物歧化酶（MnSOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和其他清除过量ROS的抗氧化酶的基因表达，从而保护BMSCs免受应激诱导的细胞凋亡。为了进一步探讨 PARK7 介导的对应激诱导的细胞凋亡的抵抗是否可以提高早期 SONFH 中 BMSC 移植的疗效，我们将过表达 PARK7 的 BMSC 移植到早期 SONFH 大鼠中。然后我们评估了移植的骨髓间充质干细胞的存活率和这些大鼠股骨头坏死区域的骨再生情况。结果表明，PARK7促进了骨坏死区BMSCs的存活，提高了BMSCs对早期SONFH的移植效果。该研究为BMSCs抵抗应激诱导的细胞凋亡、提高BMSCs对早期SONFH的移植效果提供了新的思路和方法。
Novel therapies for the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH) are urgently needed in orthopedics. Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides new strategies for treating this condition at the early stage. However, stress-induced apoptosis of BMSCs transplanted into the femoral head necrotic area limits the efficacy of BMSC transplantation. Inhibiting BMSC apoptosis is key to improving the efficacy of this procedure. In our previous studies, we confirmed that Parkinson disease protein 7 (PARK7) is active in antioxidant defense and can clear reactive oxygen species (ROS), protect the mitochondria, and impart resistance to stress-induced apoptosis in BMSCs. In this study, we investigated the mechanism driving this PARK7-mediated resistance to apoptosis in BMSCs. Our results indicate that PARK7 promoted the disintegration of nuclear factor (erythroid-derived 2)–like 2 (Nrf2)/Kelch-like echinacoside–associated protein 1 (Keap1) complex. The free Nrf2 then entered the nucleus and activated the genetic expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), and other antioxidant enzymes that clear excessive ROS, thereby protecting BMSCs from stress-induced apoptosis. To further explore whether PARK7-mediated resistance to stress-induced apoptosis could improve the efficacy of BMSC transplantation in early-stage SONFH, we transplanted BMSCs-overexpressing PARK7 into rats with early-stage SONFH. We then evaluated the survival of transplanted BMSCs and bone regeneration in the femoral head necrotic area of these rats. The results indicated that PARK7 promoted the survival of BMSCs in the osteonecrotic area and improved the transplantation efficacy of BMSCs on early-stage SONFH. This study provides new ideas and methods for resisting the stress-induced apoptosis of BMSCs and improving the transplantation effect of BMSCs on early-stage SONFH.
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影响因子：
9.2
作者：
Chen, Kai;Liu, Yuhao;He, Wei
通讯作者：
He, Wei
影响因子：
7.9
作者：
Ma, Zhanjun;Yang, Jingjing;Lu, Li
通讯作者：
Lu, Li
DOI：
10.1126/science.aam9080
发表时间：
2017-09-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Burbulla LF;Song P;Mazzulli JR;Zampese E;Wong YC;Jeon S;Santos DP;Blanz J;Obermaier CD;Strojny C;Savas JN;Kiskinis E;Zhuang X;Krüger R;Surmeier DJ;Krainc D
通讯作者：
Krainc D
影响因子：
11.4
作者：
Oh SE;Mouradian MM
通讯作者：
Mouradian MM
干细胞治疗股骨头坏死：从临床应用到相关基础研究
影响因子：
7.5
作者：
Li R;Lin QX;Liang XZ;Liu GB;Tang H;Wang Y;Lu SB;Peng J
通讯作者：
Peng J