Paper ID:8428

Induction of Matrix Metalloproteinases in Chondrocytes by Interleukin IL1β as an Osteoarthritis Model

 Ervi Afifah1, Tjandrawati Mozef2, Ferry Sandra, Seila Arumwardana1, Dwi Davidson Rihibiha1, Hayatun Nufus1, Rizal Rizal1, Annisa Amalia1, Indra Bachtiar3, Harry Murti3 & Wahyu Widowati4

 1Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163, West Java, Indonesia
2Research Center for Chemistry, Indonesian Institute of Sciences, Serpong, Indonesia
3Stem Cell and Cancer Institute, Jakarta 13210, Indonesia
4Medical Research Center, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia

E-mail: wahyu_w60@yahoo.com

Received September 25th, 2017, 1st Revision November 16th, 2017, Accept to Publish July 25th, 2018

Abstract. Osteoarthritis (OA) is a chronic disease on joint and bone due to trauma or other joint-related diseases (secondary). Synovial inflammation commonly causes disturbance in joint homeostasis which is associated with OA. Enzymes such as aggrecanase and metalloproteinease generate cartilage damage which is mediated by Interleukin (IL)-1 and Tumor Necrosis Factor (TNF). Pro-inflammatory cytokines, such as IL1β, TNF-α and IL-6, are responsible in regulation of extracelluler matrix, cartilage degradation, and apoptosis of chondrocyte. This study aimed to observe cell viability and level expression of matrix metalloproteinases (MMP1 and MMP3) and tissue inhibitor metalloproteinases (TIMP1 and TIMP2), in human chondrocyte cells (CHON002) induced by IL1β. CHON002 was induced with IL1β (0,1 ; 1 and 10 ng/ml) as an OA model. Viability was measured with a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, whilst expression of MMP1, MMP3, TIMP1, and TIMP2, was evaluated by RT-PCR. The viability of IL1β-induced CHON002 (CHON002- IL1β)  cells at day 1 and 5 showed that treatments with up to 10 ng/ml IL1β were not toxic. Expression of TIMP1 and TIMP2 in CHON-IL1β was lower compared to control, while that of MMP1 and MMP3 was higher compared to control. These results indicated that CHON002 treated with 10 ng/ml IL1β showed expression patterns consistent with chondrocyte damage, so the CHON-IL1β system may serve as a model for MMP induction in OA.

Keywords: metalloproteases, interleukin, mesenchymal stem cell, osteoarthritis, MMPs gene.

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