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Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts
| 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 https://doi.org/10.1002/art.41290. 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) |
| URI: | http://hdl.handle.net/2115/82634 |
| 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)
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Submitter: 加藤 将
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