Metallothionein 3 Promotes Osteoblast Differentiation in C2C12 Cells via Reduction of Oxidative Stress

Li, Santie; Kim, Myeong-Ji; Lee, Sungho; Jin, Litai; Cong, Weitao; Jeong, Hye Gwang; Lee, Kwang-Youl

doi:10.3390/ijms22094312

Cited by 14 publications

(14 citation statements)

References 52 publications

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“…Previous studies in our lab have demonstrated that MT3 is important for osteoblast differentiation [ 40 ], and numerous in vitro studies have shown that osteogenic factors inhibit adipogenesis, while adipogenic factors hinder osteogenesis [ 41 , 42 , 43 ]. Therefore, to explore the role of MT3 in adipocyte differentiation, we induced 3T3-L1 adipocyte differentiation and examined the levels of Mt1 , Mt2 , and Mt3 by RT-qPCR.…”

Section: Resultsmentioning

confidence: 99%

Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species

Lee

Piao

et al. 2023

Antioxidants

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Metallothionein 3 (MT3), also known as a neuronal growth-inhibitory factor, is a member of the metallothionein family and is involved in a variety of biological functions, including protection against metal toxicity and reactive oxygen species (ROS). However, less is known about the role of MT3 in the differentiation of 3T3-L1 cells into adipocytes. In this study, we observed that MT3 levels were downregulated during 3T3-L1 adipocyte differentiation. Mt3 overexpression inhibited adipocyte differentiation and reduced the levels of the adipogenic transcription factors C/EBPα and PPARγ. Further analyses showed that MT3 also suppressed the transcriptional activity of PPARγ, and this effect was not mediated by a direct interaction between MT3 with PPARγ. In addition, Mt3 overexpression resulted in a decrease in ROS levels during early adipocyte differentiation, while treatment with antimycin A, which induces ROS generation, restored the ROS levels. Mt3 knockdown, on the other hand, elevated ROS levels, which were suppressed upon treatment with the antioxidant N-acetylcysteine. Our findings indicate a previously unknown role of MT3 in the differentiation of 3T3-L1 cells into adipocytes and provide a potential novel target that might facilitate obesity treatment.

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Section: Resultsmentioning

confidence: 99%

Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species

Lee

Piao

et al. 2023

Antioxidants

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“…Certain aspects regarding the correlation between PEEK (polyether ether ketone)’s chemical structure and the oral cavity conditions have already been demonstrated to be favorable: the ether groups (R-O-R) ensure structural flexibility, ketone groups (R-CO-R) give rigidity, while the phenylene groups are chemically unreactive. Consequently, the three functional groups give PEEK (polyether ether ketone) an excellent resistance to chemical attack, good processability, toughness, and high strength [ 3 , 81 , 83 , 84 , 85 , 86 ]. It has been pointed out that PEEK (polyether ether ketone) has a good resistance to hydrolysis [ 80 , 87 ].…”

Section: Interim Prosthetic Materials Used For Obtaining Implant-supp...mentioning

confidence: 99%

Prosthetic Materials Used for Implant-Supported Restorations and Their Biochemical Oral Interactions: A Narrative Review

et al. 2022

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The purpose of this study is to outline relevant elements regarding the biochemical interactions between prosthetic materials used for obtaining implant-supported restorations and the oral environment. Implant-supported prostheses have seen unprecedented development in recent years, benefiting from the emergence of both new prosthetic materials (with increased biocompatibility and very good mechanical behavior), and computerized manufacturing technologies, which offer predictability, accuracy, and reproducibility. On the other hand, the quality of conventional materials for obtaining implant-supported prostheses is acknowledged, as they have already proven their clinical performance. The properties of PMMA (poly (methyl methacrylate))—which is a representative interim material frequently used in prosthodontics—and of PEEK (polyether ether ketone)—a biomaterial which is placed on the border between interim and final prosthetic use—are highlighted in order to illustrate the complex way these materials interact with the oral environment. In regard to definitive prosthetic materials used for obtaining implant-supported prostheses, emphasis is placed on zirconia-based ceramics. Zirconia exhibits several distinctive advantages (excellent aesthetics, good mechanical behavior, biocompatibility), through which its clinical applicability has become increasingly wide. Zirconia’s interaction with the oral environment (fibroblasts, osteoblasts, dental pulp cells, macrophages) is presented in a relevant synthesis, thus revealing its good biocompatibility.

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“…ROS is the main type of free radical involved in the destruction of bone remodeling 5 . ROS inhibits the expression of Runt‐related transcription factor‐2 (Runx2) and osterix, reducing osteogenic activity, while promoting the expression of osteoclast markers such as C‐Fos, Nuclear Factor of Activated T cells‐1 (NFATc1), and Tartrate Resistant Acid Phosphatase (TRAP) 6,7 . ROS may enhance the response of osteoclast precursors to Receptor Activator of NF‐κB Ligand (RANKL), and induce the production of additional osteoclastic factors, such as IL‐1, IL‐6, and IL‐7 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Induced Osteocyte Apoptosis in Steroid‐Induced Femoral Head Osteonecrosis through ROS‐Mediated Oxidative Stress

Zhang,

Yang,

et al. 2024

Orthopaedic Surgery

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ObjectiveGlucocorticoid (GC) overuse is strongly associated with steroid‐induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)‐induced oxidative stress on osteocyte apoptosis and the underlying mechanisms.MethodsTen patients with SINFH and 10 patients with developmental dysplasia of the hips (DDH) were enrolled in our study. Sixty rats were randomly assigned to the Control, Dex, Dex + N‐Acetyl‐L‐cysteine (NAC), Dex + Dibenziodolium chloride (DPI), NAC, and DPI groups. Magnetic resonance imaging (MRI) was used to examine edema in the femoral head of rats. Histopathological staining was performed to assess osteonecrosis. Immunofluorescence staining with TUNEL and 8‐OHdG was conducted to evaluate osteocyte apoptosis and oxidative damage. Immunohistochemical staining was carried out to detect the expression of NOX1, NOX2, and NOX4. Viability and apoptosis of MLO‐Y4 cells were measured using the CCK‐8 assay and TUNEL staining. 8‐OHdG staining was conducted to detect oxidative stress. 2′,7′‐Dichlorodihydrofluorescein diacetate (DCFH‐DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO‐Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one‐way analysis of variance (ANOVA).ResultsIn patients and the rat model, hematoxylin–eosin (HE) staining revealed a significantly higher rate of empty lacunae in the SINFH group than in the DDH group. Immunofluorescence staining indicated a significant increase in TUNEL‐positive cells and 8‐OHdG‐positive cells in the SINFH group compared to the DDH group. Immunohistochemical staining demonstrated a significant increase in the expression of NOX1, NOX2, and NOX4 proteins in SINFH patients compared to DDH patients. Moreover, immunohistochemical staining showed a significant increase in the proportion of NOX2‐positive cells compared to the Control group in the femoral head of rats. In vitro, Dex significantly inhibited the viability of osteocyte cells and induced apoptosis. After Dex treatment, the intracellular ROS level increased. However, Dex treatment did not alter the expression of NOX proteins in vitro. Additionally, NAC and DPI inhibited the generation of intracellular ROS and partially alleviated osteocyte apoptosis in vivo and in vitro.ConclusionThis study demonstrates that GC promotes apoptosis of osteocyte cells through ROS‐induced oxidative stress. Furthermore, we found that the increased expression of NOXs induced by GC serves as an important source of ROS generation.

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Metallothionein 3 Promotes Osteoblast Differentiation in C2C12 Cells via Reduction of Oxidative Stress

Cited by 14 publications

References 52 publications

Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species

Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species

Prosthetic Materials Used for Implant-Supported Restorations and Their Biochemical Oral Interactions: A Narrative Review

Dexamethasone Induced Osteocyte Apoptosis in Steroid‐Induced Femoral Head Osteonecrosis through ROS‐Mediated Oxidative Stress

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