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CPT1A 介导的脂肪酸氧化促进类风湿关节炎前体细胞破骨细胞融合。

CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Arthritis.

机构信息

The Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Department of Rheumatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

出版信息

Front Immunol. 2022 Feb 22;13:838664. doi: 10.3389/fimmu.2022.838664. eCollection 2022.

DOI:10.3389/fimmu.2022.838664
PMID:35273614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8902079/
Abstract

The overproduction of osteoclasts, leading to bone destruction in patients with rheumatoid arthritis (RA), is well established. However, little is known about the metabolic dysfunction of osteoclast precursors (OCPs) in RA. Herein, we show that increasing fatty acid oxidation (FAO) induces OCP fusion. Carnitine palmitoyltransferase IA (CPT1A), which is important for carnitine transportation and is involved in FAO in the mitochondria, is upregulated in RA patients. This metabolic change further increases the expression of clathrin heavy chain (CLTC) and clathrin light chain A (CLTA) by enhancing the binding of the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) to the promoters of and . This drives clathrin-dependent endocytosis pathway, which attenuates fusion receptors in the cellular membrane and contributes to increased podosome structure formation. This study reveals a new mechanism through which FAO metabolism participates in joint destruction in RA and provides a novel therapeutic direction for the development of drugs against bone destruction in patients with RA.

摘要

破骨细胞的过度产生导致类风湿关节炎（RA）患者的骨质破坏已得到充分证实。然而，人们对 RA 中破骨细胞前体（OCP）的代谢功能障碍知之甚少。在此，我们表明，增加脂肪酸氧化（FAO）可诱导 OCP 融合。肉碱棕榈酰转移酶 IA（CPT1A）在 RA 患者中上调，其对于肉碱转运很重要，并且在线粒体中参与 FAO。这种代谢变化通过增强转录因子 CCAAT/增强子结合蛋白β（C/EBPβ）与 和 的启动子的结合，进一步增加网格蛋白重链（CLTC）和网格蛋白轻链 A（CLTA）的表达。这驱动网格蛋白依赖性内吞作用途径，削弱细胞内膜中的融合受体，并有助于增加破骨细胞足突结构的形成。这项研究揭示了 FAO 代谢参与 RA 关节破坏的新机制，并为开发针对 RA 患者骨质破坏的药物提供了新的治疗方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/050dd78572a8/fimmu-13-838664-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/023c932cd650/fimmu-13-838664-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/bba5c6bec7d0/fimmu-13-838664-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/25b8e2fe45a4/fimmu-13-838664-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/b68a0ba288f5/fimmu-13-838664-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/89499a4a9a37/fimmu-13-838664-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/050dd78572a8/fimmu-13-838664-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/023c932cd650/fimmu-13-838664-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/bba5c6bec7d0/fimmu-13-838664-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/25b8e2fe45a4/fimmu-13-838664-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/b68a0ba288f5/fimmu-13-838664-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/89499a4a9a37/fimmu-13-838664-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba17/8902079/050dd78572a8/fimmu-13-838664-g006.jpg

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