PMID- 33827262
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210507
IS  - 2046-3758 (Print)
IS  - 2046-3758 (Electronic)
IS  - 2046-3758 (Linking)
VI  - 10
IP  - 4
DP  - 2021 Apr
TI  - Advanced oxidation protein products induce inflammatory responses and invasive 
      behaviour in fibroblast-like synoviocytes via the RAGE-NF-kappaB pathway.
PG  - 259-268
LID - 10.1302/2046-3758.104.BJR-2020-0085.R2 [doi]
AB  - AIMS: Rheumatoid arthritis (RA), which mainly results from fibroblast-like 
      synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation 
      protein products (AOPPs), which are proinflammatory mediators and a novel 
      biomarker of oxidative stress, have been observed to accumulate significantly in 
      the serum of RA patients. Here, we present the first investigation of the effects 
      of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced 
      inflammatory responses and invasive behaviour. METHODS: We used different 
      concentrations of AOPPs (50 to 200 microg/ml) to treat RA-FLSs. Cell migration and 
      invasion and the expression levels of tumour necrosis factor-alpha (TNF-alpha), 
      interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were 
      investigated. Western blot and immuno fl uorescence were used to analyze nuclear 
      factor-kappaB (NF-kappaB) activation. RESULTS: AOPPs promoted RA-FLS migration and 
      invasion in vitro and signi fi cantly induced the messenger RNA (mRNA) and protein 
      expression of TNF-alpha, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. 
      Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-kappaB 
      (NF-kappaB) p65 protein, which triggered inhibitory kappa B-alpha (IkappaBalpha) degradation, 
      NF-kappaB p65 protein phosphorylation, and NF-kappaB p65 translocation into the nucleus. 
      Furthermore, treatment with a neutralizing antibody specific to receptor for 
      advanced glycation end products (RAGE) signi fi cantly suppressed aggressive 
      behaviour and inflammation, decreased TNF-alpha, IL-6, MMP-3, and MMP-13 expression, 
      and blocked AOPP-induced NF-kappaB pathway activation. CONCLUSION: The results 
      indicate that AOPPs can enhance aggressive behaviour and the inflammatory 
      response in RA-FLSs via the RAGE-NF-kappaB pathway. These results present AOPPs as a 
      new class of potentially important mediators of progressive disease in RA 
      patients. Cite this article: Bone Joint Res 2021;10(4):259-268.
FAU - Lou, Aiju
AU  - Lou A
AD  - Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical 
      University, Guangdong, China.
AD  - Department of Rheumatology and Immunology, Liwan Central Hospital of Guangzhou, 
      Guangzhou, Guangdong, China.
FAU - Wang, Le
AU  - Wang L
AD  - Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, Guangdong, China.
AD  - Medical Technology and Related Equipment Research for Spinal Injury Treatment, 
      City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical 
      University, Guangzhou, Guangdong, China.
FAU - Lai, Weinan
AU  - Lai W
AD  - Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical 
      University, Guangdong, China.
FAU - Zhu, DingJi
AU  - Zhu D
AD  - Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical 
      University, Guangdong, China.
FAU - Wu, Weirong
AU  - Wu W
AD  - Department of Rheumatology and Immunology, Liwan Central Hospital of Guangzhou, 
      Guangzhou, Guangdong, China.
FAU - Wang, Zhao
AU  - Wang Z
AD  - Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, Guangdong, China.
AD  - Medical Technology and Related Equipment Research for Spinal Injury Treatment, 
      City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical 
      University, Guangzhou, Guangdong, China.
FAU - Cai, Zihong
AU  - Cai Z
AD  - Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, Guangdong, China.
AD  - Medical Technology and Related Equipment Research for Spinal Injury Treatment, 
      City Key Laboratory, The Third Affiliated Hospital of Guangzhou Medical 
      University, Guangzhou, Guangdong, China.
FAU - Yang, Min
AU  - Yang M
AD  - Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical 
      University, Guangdong, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Bone Joint Res
JT  - Bone & joint research
JID - 101586057
PMC - PMC8077182
OTO - NOTNLM
OT  - Advanced oxidation protein products
OT  - Fibroblast-like synoviocyte
OT  - Receptor for advanced glycation end products
OT  - Rheumatoid arthritis
EDAT- 2021/04/09 06:00
MHDA- 2021/04/09 06:01
PMCR- 2021/04/01
CRDT- 2021/04/08 05:26
PHST- 2021/04/08 05:26 [entrez]
PHST- 2021/04/09 06:00 [pubmed]
PHST- 2021/04/09 06:01 [medline]
PHST- 2021/04/01 00:00 [pmc-release]
AID - BJR-10-259 [pii]
AID - 10.1302/2046-3758.104.BJR-2020-0085.R2 [doi]
PST - ppublish
SO  - Bone Joint Res. 2021 Apr;10(4):259-268. doi: 
      10.1302/2046-3758.104.BJR-2020-0085.R2.