Histone H3K9 methylation is involved in temporomandibular joint osteoarthritis

Ukita,Mayumi; Matsushita,Kenji; Tamura,Masato; Yamaguchi,Taihiko

doi:10.3892/ijmm.2019.4446

Histone H3K9 methylation is involved in temporomandibular joint osteoarthritis

Authors:
- Mayumi Ukita
- Kenji Matsushita
- Masato Tamura
- Taihiko Yamaguchi
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Affiliations: Crown and Bridge Prosthodontics, Department of Oral Functional Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060‑8586, Japan, Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi 474‑8511, Japan, Biochemistry and Molecular Biology, Department of Oral Health Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060‑8586, Japan
Published online on: December 27, 2019 https://doi.org/10.3892/ijmm.2019.4446
Pages: 607-614

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Abstract

The morbidity of temporomandibular joint osteoarthritis (TMJOA) increases with age. Condylar articular cartilage degradation, which causes TMJOA, is known to be involved in articular chondrocyte metabolic imbalances in the temporomandibular joint (TMJ) and in other joints of the body. Epigenetic regulation, such as the chemical modification of DNA and histones, is implicated in cartilage homeostasis. However, few studies have been conducted on the epigenetic regulation of condylar articular cartilage degradation. The present study investigated the regulation of histone H3 lysine 9 (H3K9) methylation and its effects on the pathogenesis of degenerative TMJ cartilage disorders. The histone H3K9 methylation level was decreased in degenerated condylar articular cartilage in aged mice. Treatment with chaetocin (a selective H3K9 methylation inhibitor) reduced cell viability and promoted caspase‑3/7 activity in ATDC5 mouse chondroprogenitor cells. The inhibition of H3K9 methylation increased matrix metalloproteinase (Mmp)1 and Mmp13 mRNA expression in these cells. Furthermore, the expression levels of Sox9 and collagen α1(II) (Col2a1) mRNA, which are anabolic factors for chondrogenic differentiation, were also decreased by treatment with chaetocin, which is an inhibitor of histone methyltransferases. These results indicated that histone H3K9 methylation regulates chondrocyte homeostasis in terms of cell growth, apoptosis and gene expression, and highlighted a possible future therapy option for TMJOA.

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