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Anti‐arthritic effects of melatonin through blockade of cytonuclear shift of MMP‐13
Author(s) -
Hong Yunkyung,
Hong Yonggeun
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb430
Subject(s) - melatonin , matrix metalloproteinase , chemistry , medicine , proteoglycan , cartilage , endocrinology , viability assay , cell , biochemistry , biology , anatomy , extracellular matrix
No curative treatments for osteoarthritic cartilage have been reported. The aim of the present study was to determine the therapeutic effects of melatonin on osteoarthritic chondrocytes. Chondrocytes were isolated from the cartilage specimens of the neonatal rats, cultured in monolayer, and treated with TNF‐α (10 ng/mL) repeatedly. We added DMSO combined with or without melatonin to medium. Caspase‐3 cleavage was induced by TNF‐α within 15 min, which is consistent with reduced cell viability. Co‐treatment of TNF‐α with DMSO induced not only increases of MMP‐13, both full length pro‐ and active proteins, but also shift of cytosolic MMP‐13 into the nucleus. Also there were metabolic disruption of COL2A1, proteoglycan loss, their atypical distribution, and excessive Ca 2+ deposit. Melatonin, which was treated at the concentration of 1 nM, restored aberrant levels of COL2A1. Cytonuclear translocation of MMP‐13 was blocked by nanomolar concentration of melatonin partially, although its level was still remained high. Melatonin induced increase of the amount of proteoglycan with well‐distribution in chondrocytes. Moreover, the number of cells containing Ca 2+ crystals decreased by melatonin treatment. Based on these results, we suggest that melatonin might be able to inhibit turning on of catabolic switch through regulation of MMP‐13 localization. Funding: 2012R1A1A2005089, 2013R1A2A2A01067169, KGM4611512