Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis

Takashi Izawa, Hiroki Mori, Tekehiro Shinohara, Akiko Mino-Oka, Islamy Rahma Hutami, Akihiko Iwasa, Eiji Tanaka

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive degradation of cartilage and changes in subchondral bone. It is also one of the most serious subgroups of temporomandibular disorders. Rebamipide is a gastroprotective agent that is currently used for the treatment of gastritis and gastric ulcers. It scavenges reactive oxygen radicals and has exhibited anti-inflammatory potential. The aim of this study was to investigate the impact of rebamipide both in vivo and in vitro on the development of cartilage degeneration and osteoclast activity in an experimental murine model of TMJ-OA, and to explore its mode of action. Oral administration of rebamipide (0.6 mg/kg and 6 mg/kg) was initiated 24 h after TMJ-OA was induced, and was maintained daily for four weeks. Rebamipide treatment was found to attenuate cartilage degeneration, to reduce the number of apoptotic cells, and to decrease the expression levels of matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in TMJ-OA cartilage in a dose-dependent manner. Rebamipide also suppressed the activation of transcription factors (e.g., NF-κB, NFATc1) and mitogen-activated protein kinases (MAPK) by receptor activator of nuclear factor kappa-B ligand (RANKL) to inhibit the differentiation of osteoclastic precursors, and disrupted the formation of actin rings in mature osteoclasts. Together, these results demonstrate the inhibitory effects of rebamipide on cartilage degradation in experimentally induced TMJ-OA. Furthermore, suppression of oxidative damage, restoration of extracellular matrix homeostasis of articular chondrocytes, and reduced subchondral bone loss as a result of blocked osteoclast activation suggest that rebamipide is a potential therapeutic strategy for TMJ-OA.

Original languageEnglish
Pages (from-to)e0154107
JournalPloS one
Volume11
Issue number4
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Fingerprint

RANK Ligand
osteoarthritis
Temporomandibular Joint
Osteogenesis
Osteoarthritis
cartilage
Down-Regulation
Cartilage
animal models
receptors
osteoclasts
Osteoclasts
bones
Bone
Chemical activation
stomach ulcers
gastritis
Matrix Metalloproteinase 13
degradation
chondrocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis. / Izawa, Takashi; Mori, Hiroki; Shinohara, Tekehiro; Mino-Oka, Akiko; Hutami, Islamy Rahma; Iwasa, Akihiko; Tanaka, Eiji.

In: PloS one, Vol. 11, No. 4, 01.01.2016, p. e0154107.

Research output: Contribution to journalArticle

Izawa, Takashi ; Mori, Hiroki ; Shinohara, Tekehiro ; Mino-Oka, Akiko ; Hutami, Islamy Rahma ; Iwasa, Akihiko ; Tanaka, Eiji. / Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis. In: PloS one. 2016 ; Vol. 11, No. 4. pp. e0154107.
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