Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization

Matthiesen, Cecilie Linneberg; Hu, Lili; Tørslev, Astrid S.; Poulsen, Ebbe Toftgaard; Larsen, Ulrike G.; Kjær-Sørensen, Kasper; Thomsen, Jesper Skovhus; Brüel, Annemarie; Enghild, Jan J.; Oxvig, Claus; Petersen, Steen V.

doi:10.1016/j.freeradbiomed.2021.01.027

Cited by 10 publications

(5 citation statements)

References 68 publications

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“…SOD3, an extracellular antioxidant enzyme, efficiently converts superoxide free radicals into hydrogen peroxide, thus preventing the accumulation of ROS [ 30 ]. Mice deficient in SOD3 exhibited increased synovial inflammation, cartilage degradation, and bone erosion, whereas SOD3 overexpression mitigated these effects, reducing disease severity [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment

Cao,

Li,

Zhang

et al. 2024

J Nanobiotechnol

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Background and aims Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of joint cartilage, synovial inflammation, and subchondral bone hyperplasia. The synovial tissue plays a pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released by cells into the extracellular space, are crucial in mediating intercellular communication and facilitating the exchange of information between tissues. Our study aimed to devise a hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) to protect cartilage and introduce a novel, effective approach for OA treatment. Materials and methods We analyzed single-cell sequencing data from 4247 cells obtained from the GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), and assays to measure oxidative stress levels were employed to validate the cartilage-protective properties of the identified key protein, SOD3. In vivo, OA mice received intra-articular injections of S-EXOs bearing hydrogel microspheres, and the effectiveness was assessed using safranine O (S.O) staining and IF. Results Single-cell sequencing data analysis suggested that the synovium influences cartilage via the exocrine release of SOD3. Our findings revealed that purified S-EXOs enhanced antioxidant capacity of chondrocytes, and maintained extracellular matrix metabolism stability. The S-EXO group showed a significant reduction in mitoROS and ROS levels by 164.2% (P < 0.0001) and 142.7% (P < 0.0001), respectively, compared to the IL-1β group. Furthermore, the S-EXO group exhibited increased COL II and ACAN levels, with increments of 2.1-fold (P < 0.0001) and 3.1-fold (P < 0.0001), respectively, over the IL-1β group. Additionally, the S-EXO group showed a decrease in MMP13 and ADAMTS5 protein expression by 42.3% (P < 0.0001) and 44.4% (P < 0.0001), respectively. It was found that S-EXO-containing hydrogel microspheres could effectively deliver SOD3 to cartilage and significantly mitigate OA progression. The OARSI score in the S-EXO microsphere group markedly decreased (P < 0.0001) compared to the OA group. Conclusion The study demonstrated that the S-EXOs secreted by synovial fibroblasts exert a protective effect on chondrocytes, and microspheres laden with S-EXOs offer a promising therapeutic alternative for OA treatment.

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Section: Discussionmentioning

confidence: 99%

Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment

Cao,

Li,

Zhang

et al. 2024

J Nanobiotechnol

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“…The enzyme activity assay showed that SOD was markedly decreased, whereas MDA and CAT were significantly increased. Superoxide dismutase represents the ability of the body to effectively scavenge free radicals [61]. CAT displays the activity of catalase in the body [62], whereas MDA is the product of lipid oxidation, which can reflect the degree of lipid peroxidation in the body and thus indirectly indicate the degree of cell damage [63].…”

Section: Discussionmentioning

confidence: 99%

Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress

Fan

Shen

Jia

et al. 2022

Toxics

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Pentachloronitrobenzene (PCNB) is an organochlorine protective fungicide mainly used as a soil and seed fungicide. Currently, there are few reports on the toxicity of PCNB to zebrafish embryo. Here, we evaluated the toxicity of PCNB in aquatic vertebrates using a zebrafish model. Exposure of zebrafish embryos to PCNB at concentrations of 0.25 mg/L, 0.5 mg/L, and 0.75 mg/L from 6 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent. We found that PCNB increased reactive oxygen species stress levels in zebrafish, increased malondialdehyde (MDA) content and catalase (CAT) activity, and decreased superoxide dismutase (SOD) activity. The increased level of oxidative stress reduced the proliferation ability of zebrafish cardiomyocytes, and the expressions of zebrafish proliferation-related genes such as cdk-2, cdk-6, ccnd1, and ccne1 were significantly down-regulated. Astaxanthin (AST) attenuates PCNB-induced reduction in zebrafish cardiomyocyte proliferation by reducing oxidative stress levels. Our study shows that PCNB can cause severe oxidative stress in zebrafish, thereby reducing the proliferative capacity of cardiomyocytes, resulting in zebrafish cardiotoxicity.

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“…90 SOD3a and SOD3b genes are present in different organs of the adult zebrafish and are required for normal bone homeostasis and mineralisation. 91 In addition, Sun et al cloned the MnSOD gene from Acipenser ruthenus that displayed highest expression in the brain and liver. Further studies also revealed the involvement of MnSOD in the stress response and antioxidant process of Aeromonas hydrophila infection and hypoxia.…”

Section: Lemmens Et Al Had Shown That Overexpression Of Sod1 In Mutantsmentioning

confidence: 99%

“…In mammalian macrophages and neutrophils, LPS induced the up‐regulation of SOD2 expression, while SOD2 knockdown increased bacterial burden 90 . SOD3a and SOD3b genes are present in different organs of the adult zebrafish and are required for normal bone homeostasis and mineralisation 91 . In addition, Sun et al cloned the MnSOD gene from Acipenser ruthenus that displayed highest expression in the brain and liver.…”

Section: Cellular Sources and Regulation Of Rosmentioning

confidence: 99%

Signalling regulation of reactive oxygen species in fish inflammation

Gao,

Zhao,

Shi

et al. 2024

Reviews in Aquaculture

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Reactive oxygen species (ROS), which are key cellular signalling molecules, are reactive chemicals containing oxygen. Cell survival or death is a critical issue in the inflammatory response. Accumulation of ROS involves ROS generation and scavenging, which determine ROS homeostasis. Understanding the roles of ROS in modulating the inflammatory response in fish is vital for helping protect fish from the damage of water pollutants in harsh environmental conditions. ROS‐related key genes and signalling pathways are relatively conserved in fish but vary among different species. Recent frequent incidences of fish diseases have posed a considerable challenge to large‐scale aquaculture. ROS is important in stress perception, integration of diverse stress‐responsive signalling networks, and activation of animal defence mechanisms, which frequently occur during inflammation in fish. This review summarises recent studies on ROS signalling pathways during inflammation in fish. Furthermore, it examines the relationship between ROS and inflammation in fish. This review may contribute to the understanding of the underlying mechanisms by which ROS regulate inflammation in fish and provide suggestions for sustainable development in aquaculture.

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Superoxide dismutase 3 is expressed in bone tissue and required for normal bone homeostasis and mineralization

Cited by 10 publications

References 68 publications

Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment

Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment

Pentachloronitrobenzene Reduces the Proliferative Capacity of Zebrafish Embryonic Cardiomyocytes via Oxidative Stress

Signalling regulation of reactive oxygen species in fish inflammation

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