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Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-β/TXNIP pathway
Osteoarthritis and Cartilage ( IF 7.2 ) Pub Date : 2024-05-12 , DOI: 10.1016/j.joca.2024.05.001 Xiaohang Zheng 1 , Jianxin Qiu 1 , Jiajing Ye 1 , Yuhang Gong 1 , Ting Jiang 1 , Ning Gao 2 , Chao Jiang 1 , Binxiang Chu 1 , Weikang Zhang 1 , Ze Li 1 , Xinyu Wu 1 , Guangyong Yang 1 , Xingbing Feng 1 , Zhenghua Hong 1
Osteoarthritis and Cartilage ( IF 7.2 ) Pub Date : 2024-05-12 , DOI: 10.1016/j.joca.2024.05.001 Xiaohang Zheng 1 , Jianxin Qiu 1 , Jiajing Ye 1 , Yuhang Gong 1 , Ting Jiang 1 , Ning Gao 2 , Chao Jiang 1 , Binxiang Chu 1 , Weikang Zhang 1 , Ze Li 1 , Xinyu Wu 1 , Guangyong Yang 1 , Xingbing Feng 1 , Zhenghua Hong 1
Affiliation
Intervertebral Disc Degeneration (IVDD) is one of the leading causes of low back pain, significantly impacting both individuals and society. This study aimed to investigate the significance of macrophage infiltration and the role of macrophage-secreted platelet-derived growth factor-BB (PDGF-BB) in IVDD progression. To confirm the protective function of macrophage-derived PDGF-BB on nucleus pulposus cells (NPCs), we employed Lysm-Cre transgenic mice to genetically ablate PDGF-B within the myeloid cells. Immunohistochemistry was utilized to detect the expression of glycolytic enzymes and pyroptosis-related proteins during the process of IVDD. Western blot, RT-PCR, ELISA and immunofluorescence were used to detect the protective effect of recombinant PDGF-BB on NPCs. Macrophage-derived PDGF-BB deficiency resulted in the loss of NPCs and the increased ossification of cartilage endplates during lumbar disc degeneration. Also, PDGF-BB deficiency triggered the inhibition of glycolytic enzymes’ expression and the activation of pathways related to pyroptosis in the nucleus pulposus. Mechanistically, our results suggest that PDGF-BB predominantly conveys its protective influence on NPCs through the PDGF receptor- beta (PDGFR-β)/ thioredoxin-interacting protein pathway. The absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds the potential for retarding intervertebral disc degeneration in the human body.
中文翻译:
巨噬细胞源性PDGF-BB通过PDGFR-β/TXNIP途径调节髓核细胞中糖酵解酶的表达和细胞焦亡
椎间盘退变 (IVDD) 是腰痛的主要原因之一,对个人和社会都有重大影响。本研究旨在探讨巨噬细胞浸润的意义以及巨噬细胞分泌的血小板衍生生长因子-BB (PDGF-BB) 在 IVDD 进展中的作用。为了确认巨噬细胞衍生的 PDGF-BB 对髓核细胞 (NPC) 的保护功能,我们使用 Lysm-Cre 转基因小鼠对髓系细胞内的 PDGF-B 进行基因消除。采用免疫组化方法检测IVDD过程中糖酵解酶和细胞焦亡相关蛋白的表达。采用Western blot、RT-PCR、ELISA和免疫荧光检测重组PDGF-BB对NPCs的保护作用。巨噬细胞衍生的PDGF-BB缺陷导致腰椎间盘退变过程中NPC的丢失和软骨终板的骨化增加。此外,PDGF-BB 缺乏还会引发糖酵解酶表达的抑制以及髓核焦亡相关途径的激活。从机制上讲,我们的结果表明,PDGF-BB 主要通过 PDGF 受体-β (PDGFR-β)/硫氧还蛋白相互作用蛋白途径传递其对 NPC 的保护作用。源自巨噬细胞的PDGF-BB的缺乏加速了IVDD的进展,而PDGF-BB治疗的应用具有延缓人体内椎间盘退变的潜力。
更新日期:2024-05-12
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
巨噬细胞源性PDGF-BB通过PDGFR-β/TXNIP途径调节髓核细胞中糖酵解酶的表达和细胞焦亡
椎间盘退变 (IVDD) 是腰痛的主要原因之一,对个人和社会都有重大影响。本研究旨在探讨巨噬细胞浸润的意义以及巨噬细胞分泌的血小板衍生生长因子-BB (PDGF-BB) 在 IVDD 进展中的作用。为了确认巨噬细胞衍生的 PDGF-BB 对髓核细胞 (NPC) 的保护功能,我们使用 Lysm-Cre 转基因小鼠对髓系细胞内的 PDGF-B 进行基因消除。采用免疫组化方法检测IVDD过程中糖酵解酶和细胞焦亡相关蛋白的表达。采用Western blot、RT-PCR、ELISA和免疫荧光检测重组PDGF-BB对NPCs的保护作用。巨噬细胞衍生的PDGF-BB缺陷导致腰椎间盘退变过程中NPC的丢失和软骨终板的骨化增加。此外,PDGF-BB 缺乏还会引发糖酵解酶表达的抑制以及髓核焦亡相关途径的激活。从机制上讲,我们的结果表明,PDGF-BB 主要通过 PDGF 受体-β (PDGFR-β)/硫氧还蛋白相互作用蛋白途径传递其对 NPC 的保护作用。源自巨噬细胞的PDGF-BB的缺乏加速了IVDD的进展,而PDGF-BB治疗的应用具有延缓人体内椎间盘退变的潜力。