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Open AccessArticle

Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis

1
Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA
2
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
3
Department of Pathology, College of Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 908; https://doi.org/10.3390/cells8080908
Received: 3 June 2019 / Revised: 29 July 2019 / Accepted: 15 August 2019 / Published: 16 August 2019
(This article belongs to the Section Stem Cells)
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PDF [4119 KB, uploaded 16 August 2019]
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Abstract

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis. View Full-Text
Keywords: rheumatoid arthritis; KLF2; inflammation; monocytes; osteoclasts; MMP9; conditional knockout mice rheumatoid arthritis; KLF2; inflammation; monocytes; osteoclasts; MMP9; conditional knockout mice
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Das, M.; Deb, M.; Laha, D.; Joseph, M.; Kanji, S.; Aggarwal, R.; Iwenofu, O.H.; Pompili, V.J.; Jarjour, W.; Das, H. Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis. Cells 2019, 8, 908.

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