title: Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways.
abstract: Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient and antioxidant and has been reported to exert potent immunosuppressive effects. However, the therapeutically potential of PQQ on rheumatoid arthritis (RA) has not been explored. In the present study, the anti-inflammatory effects of PQQ were investigated in interleukin (IL)-1β-treated SW982 cells, a RA-like fibroblast-like synoviocytes (FLSs) injury model. Our observations showed that pretreatment with PQQ significantly inhibited the expression of matrix metalloproteinase (MMP)-1 and MMP-3 and suppressed the production of proinflammatory mediators such as TNF-α and IL-6 in IL-1β-treated SW982 cells. The nuclear translocation of nuclear factor kappa B (NF-κB) and the phosphorylation level of p65, p38, and JNK MAP kinase pathways were also inhibited by PQQ in IL-1β-stimulated SW982 cells. To further confirm the therapeutic effects of PQQ on RA in vivo, a collagen-induced arthritis (CIA) model was used. Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of RA.
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Zhongbing
authors: Z
authors: Liu
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Chi
authors: C
authors: Sun
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Ran
authors: R
authors: Tao
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Xinbao
authors: X
authors: Xu
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors: Libin
authors: L
authors: Xu
authors: Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China.
authors: Hongbing
authors: H
authors: Cheng
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China. wangyouhua_nt@163.com.
authors: Youhua
authors: Y
authors: Wang
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China. zhangdongmei_nt@163.com.|Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China. zhangdongmei_nt@163.com.
authors: Dongmei
authors: D
authors: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000843:Ankle Joint / Q000473:pathology*; D000975:Antioxidants / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D045542:PQQ Cofactor / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; C498143:RELA protein, human; C439524:TNF protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D045542:PQQ Cofactor; D048051:p38 Mitogen-Activated Protein Kinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: P65; SW982; collagen-induced arthritis (CIA); inflammatory; pyrroloquinoline quinone (PQQ)