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1.
Aging (Albany NY) ; 15(22): 13452-13470, 2023 11 29.
Article in English | MEDLINE | ID: mdl-38032278

ABSTRACT

AIMS: The acceleration of osteoarthritis (OA) development by chondrocytes undergoing ferroptosis has been observed. Plumbagin (PLB), known for its potent antioxidant and anti-inflammatory properties, has demonstrated promising potential in the treatment of OA. However, it remains unclear whether PLB can impede the progression of temporomandibular joint osteoarthritis (TMJOA) through the regulation of ferroptosis. The study aims to investigate the impact of ferroptosis on TMJOA and assess the ability of PLB to modulate the inhibitory effects of ferroptosis on TMJOA. MATERIALS AND METHODS: The study utilized an in vivo rat model of unilateral anterior crossbite (UAC)-induced TMJOA and an in vitro study of chondrocytes exposed to H2O2 to create an OA microenvironment. Various experiments including cell viability assessment, quantitative RT-PCR, western blot analysis, histology, and immunofluorescence were conducted to examine the impact of ferroptosis on TMJOA and evaluate the potential of PLB to mitigate the inhibitory effects of ferroptosis on TMJOA. Additionally, RNA-seq and bioinformatics analysis were performed to investigate the underlying mechanism by which PLB regulates ferroptosis in TMJOA. RESULTS: Fer-1 demonstrated its potential in mitigating the advancement of TMJOA through its inhibitory effects on ferroptosis and matrix degradation in chondrocytes, thereby substantiating the role of ferroptosis in the pathogenesis of TMJOA. Furthermore, the observed protective impact of PLB on cartilage implied that PLB can modulate the inhibition of ferroptosis in TMJOA by regulating the MAPK signaling pathways. CONCLUSIONS: PLB alleviates TMJOA progression by suppressing chondrocyte ferroptosis via MAPK pathways, indicating PLB to be a potential therapeutic strategy for TMJOA.


Subject(s)
Cartilage, Articular , Ferroptosis , Osteoarthritis , Rats , Animals , Chondrocytes/metabolism , Hydrogen Peroxide/pharmacology , Cartilage, Articular/metabolism , Temporomandibular Joint/metabolism , Temporomandibular Joint/pathology , Signal Transduction , Osteoarthritis/metabolism
2.
Aging (Albany NY) ; 15(11): 4861-4874, 2023 06 05.
Article in English | MEDLINE | ID: mdl-37277114

ABSTRACT

Osteoarthritis (OA) is a chronic and complicated degenerative disease for which there is currently no effective treatment. Isoorientin (ISO) is a natural plant extract that has antioxidant activity and could be used to treat OA. However, due to a lack of research, it has not been widely used. In this study, we investigated the protective effects and molecular mechanisms of ISO on H2O2-induced chondrocytes, a widely used cell model for OA. Based on RNA-seq and bioinformatics, we discovered that ISO significantly increased the activity of chondrocytes induced by H2O2, which was associated with apoptosis and oxidative stress. Furthermore, the combination of ISO and H2O2 significantly reduced apoptosis and restored mitochondrial membrane potential (MMP), which may be achieved by inhibiting apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, ISO increased superoxide dismutase (SOD), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) and reduced malondialdehyde (MDA) levels. Finally, ISO inhibited H2O2-induced intracellular reactive oxygen species (ROS) in chondrocytes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathways. This study establishes a theoretical framework for ISO's ability to inhibit OA in vitro models.


Subject(s)
Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Hydrogen Peroxide/toxicity , Mitogen-Activated Protein Kinases/metabolism , Chondrocytes/metabolism , Oxidative Stress , Antioxidants/pharmacology , Antioxidants/metabolism , Reactive Oxygen Species/metabolism , Apoptosis , NF-E2-Related Factor 2/metabolism
3.
Acta Odontol Scand ; 75(8): 595-602, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28814141

ABSTRACT

OBJECTIVES: Our main aim was to evaluate the effects of calcitonin (CT) on orthodontic tooth movement (OTM) and orthodontic root resorption in a rat model. MATERIAL AND METHODS: Eighty male Wistar rats were randomly divided into five groups. Rats in the negative control group were not given any appliances or injections. All the remaining rats were used to establish a model of OTM. The positive control group were then injected with normal saline, while rats in the three experimental groups were injected with 0.2 IU, 1 IU or 5 IU/kg/day CT. Nickel-titanium closed-coil springs were used to deliver an initial 50 g mesial force to the left maxillary first molar for 14 days in rats in the positive control group and the experimental groups. Each group was randomly subdivided into two groups, one for analysis of tooth movement, tissue changes and tartrate-resistant acid phosphatase (TRAP)-positive cells in alveolar bone, the other to examine root resorption by scanning electron microscopy. RESULTS: The OTM distance, the number of force-induced osteoclasts and root resorption areas were significantly decreased in CT-injected rats in a dose-dependent manner. CONCLUSIONS: Administration of CT reduces the root resorption area and may therefore be effective as a novel adjunctive orthodontic approach to diminish undesired tooth movement via enhancing anchorage or preventing relapse after OTM.


Subject(s)
Calcitonin/pharmacology , Osteoclasts/drug effects , Root Resorption/drug therapy , Tartrate-Resistant Acid Phosphatase/pharmacology , Tooth Root/drug effects , Animals , Male , Microscopy, Electron, Scanning , Molar/drug effects , Nickel , Rats , Rats, Wistar , Titanium
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