RRC ID 51720
Author Izawa T, Mori H, Shinohara T, Mino-Oka A, Hutami IR, Iwasa A, Tanaka E.
Title Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis.
Journal PLoS One
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.
Volume 11(4)
Pages e0154107
Published 2016-1-1
DOI 10.1371/journal.pone.0154107
PII PONE-D-15-51102
PMID 27123995
PMC PMC4849711
MeSH Administration, Oral Alanine / analogs & derivatives* Alanine / pharmacology Animals Anti-Inflammatory Agents / pharmacology* Apoptosis / drug effects Arthritis, Experimental / drug therapy* Arthritis, Experimental / genetics Arthritis, Experimental / metabolism Arthritis, Experimental / pathology Cartilage, Articular / drug effects Cartilage, Articular / metabolism Cartilage, Articular / pathology Chondrocytes / drug effects Chondrocytes / metabolism Chondrocytes / pathology Drug Administration Schedule Extracellular Matrix / drug effects Extracellular Matrix / metabolism Extracellular Matrix / pathology Gene Expression Regulation Mandibular Condyle / drug effects Mandibular Condyle / metabolism Mandibular Condyle / pathology Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism Mice Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism NF-kappa B / genetics NF-kappa B / metabolism NFATC Transcription Factors / genetics NFATC Transcription Factors / metabolism Nitric Oxide Synthase Type II / genetics Nitric Oxide Synthase Type II / metabolism Osteoarthritis / drug therapy* Osteoarthritis / genetics Osteoarthritis / metabolism Osteoarthritis / pathology Osteoclasts / drug effects Osteoclasts / metabolism Osteoclasts / pathology Osteogenesis / drug effects* Osteogenesis / genetics Quinolones / pharmacology* RANK Ligand / genetics RANK Ligand / metabolism Signal Transduction Temporomandibular Joint / drug effects Temporomandibular Joint / metabolism Temporomandibular Joint / pathology Temporomandibular Joint Disorders / drug therapy* Temporomandibular Joint Disorders / genetics Temporomandibular Joint Disorders / metabolism Temporomandibular Joint Disorders / pathology
IF 2.74
Times Cited 7
Human and Animal Cells MKN45(RCB1001)