HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Hokkaido University Hospital >
Peer-reviewed Journal Articles, etc >

Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts

Files in This Item:
Arthritis Rheumatol_72_1493.pdfMain text 6.78 MBPDFView/Open
art41290-sup-0001-supinfo.docxSupplementary Material17.61 MBMicrosoft Word XMLView/Open
Please use this identifier to cite or link to this item:

Title: Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts
Authors: Lee, Wen Shi Browse this author
Kato, Masaru Browse this author →KAKEN DB
Sugawara, Eri Browse this author
Kono, Michihiro Browse this author
Kudo, Yuki Browse this author
Kono, Michihito Browse this author →KAKEN DB
Fujieda, Yuichiro Browse this author →KAKEN DB
Bohgaki, Toshiyuki Browse this author →KAKEN DB
Amengual, Olga Browse this author →KAKEN DB
Oku, Kenji Browse this author →KAKEN DB
Yasuda, Shinsuke Browse this author →KAKEN DB
Onodera, Tomohiro Browse this author →KAKEN DB
Iwasaki, Norimasa Browse this author →KAKEN DB
Atsumi, Tatsuya Browse this author →KAKEN DB
Issue Date: Sep-2020
Publisher: John Wiley & Sons
Journal Title: Arthritis & rheumatology
Volume: 72
Issue: 9
Start Page: 1493
End Page: 1504
Publisher DOI: 10.1002/art.41290
Abstract: Objective Optineurin (OPTN) is an autophagy adaptor/receptor that acts as an intrinsic negative regulator of osteoclast differentiation.RANKLexpressed by rheumatoid arthritis synovial fibroblasts (RASFs) is primarily responsible for the development of bone erosions in patients withRA. The aim of the present study was to explore the role ofOPTNin the pathogenesis of joint destruction inRA. Methods RASFs were left untreated or incubated with tumor necrosis factor (TNF) or interferon-gamma (IFN gamma), and expression ofOPTNbyRASFs was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Expression ofRANKLand osteoprotegerin (OPG) was evaluated in cultures ofOPTN-reducedRASFs with or withoutTNForIFN gamma treatment.OPTN-reducedRASFs were cocultured with monocytes and stained for tartrate-resistant acid phosphatase (TRAP). I kappa B alpha,NF-kappa B1, and RelA protein levels were measured to evaluateNF-kappa B signaling. Expression of messengerRNA(mRNA) for matrix metalloproteinase 3 (MMP3), interleukin-6 (IL6),GATAbinding protein 3 (GATA3), carbohydrate sulfotransferase 15 (CHST15), hyaluronan synthase 1 (HAS1), andGATA1was analyzed byRT-qPCR. Results InRASFs incubated withTNForIFN gamma,OPTNexpression was up-regulated andRANKLexpression was increased, and these effects were further pronounced inOPTN-reducedRASFs (allP< 0.05 versus controls).OPG mRNAlevels remained unchanged. Monocytes cocultured withOPTN-reducedRASFs differentiated to a greater extent intoTRAP+ multinucleated cells compared to monocytes cocultured with controlRASFs (P< 0.05). I kappa B alpha degradation and nuclearNF-kappa B1 expression followingTNFtreatment were both prolonged inOPTN-reducedRASFs (eachP< 0.05 versus controls).MMP3mRNAlevels were up-regulated, whileGATA3,CHST15, andHAS1mRNAlevels were down-regulated inOPTN-reducedRASFs (eachP< 0.05 versus controls). Conclusion OPTNplays a protective role inRAwhen it is up-regulated inRASFs in the presence of proinflammatory cytokines. Absence ofOPTNmight worsenRAby generating a joint-destructive state, as indicated by evidence of increasedRANKLexpression onRASFs and subsequent osteoclast differentiation.
Rights: This is the peer reviewed version of the following article: Lee, W.S., Kato, M., Sugawara, E., Kono, M., Kudo, Y., Kono, M., Fujieda, Y., Bohgaki, T., Amengual, O., Oku, K., Yasuda, S., Onodera, T., Iwasaki, N. and Atsumi, T. (2020), Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts. Arthritis Rheumatol, 72: 1493-1504., which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Type: article (author version)
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 加藤 将

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University