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      Excavating bioactivities of nanozyme to remodel microenvironment for protecting chondrocytes and delaying osteoarthritis

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          Abstract

          Osteoarthritis (OA) is the main cause of disability in the elderly. Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease, and reduce the probability of joint replacement. However, there is to date no effective intervention for early and middle-stage OA. OA microenvironment mainly destroys the balance of oxidative stress, extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors. Herein, hollow Prussian blue nanozymes (HPBzymes) were designed via a modified hydrothermal template-free method. The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA. The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo, remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species (ROS) and Rac1/nuclear factor kappa-B (NF-κB) signaling in a rat model. HPBzyme significantly diminished interleukin (IL)-1β-stimulated inflammation, extracellular matrix degradation, and apoptosis of human chondrocytes. HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB. Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases. This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.

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          Highlights

          • HPBzymes are synthesized via a modified hydrothermal template-free method.

          • HPBzymes protectchondrocytes and delay the progression of traumatic OA.

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          Most cited references77

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          Osteoarthritis

          Osteoarthritis is a leading cause of disability and source of societal cost in older adults. With an ageing and increasingly obese population, this syndrome is becoming even more prevalent than in previous decades. In recent years, we have gained important insights into the cause and pathogenesis of pain in osteoarthritis. The diagnosis of osteoarthritis is clinically based despite the widespread overuse of imaging methods. Management should be tailored to the presenting individual and focus on core treatments, including self-management and education, exercise, and weight loss as relevant. Surgery should be reserved for those that have not responded appropriately to less invasive methods. Prevention and disease modification are areas being targeted by various research endeavours, which have indicated great potential thus far. This narrative Seminar provides an update on the pathogenesis, diagnosis, management, and future research on osteoarthritis for a clinical audience.
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            The NF-kappaB family of transcription factors and its regulation.

            Nuclear factor-kappaB (NF-kappaB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappaB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappaB proteins (IkappaBs), which retain inactive NF-kappaB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappaB activation converge on the IkappaB kinase (IKK) complex, which is responsible for IkappaB phosphorylation and is essential for signal transduction to NF-kappaB. Additional regulation of NF-kappaB activity is achieved through various post-translational modifications of the core components of the NF-kappaB signaling pathways. In addition to cytosolic modifications of IKK and IkappaB proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappaB response. This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation.
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              Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.

              Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                29 January 2021
                August 2021
                29 January 2021
                : 6
                : 8
                : 2439-2451
                Affiliations
                [a ]Department of Orthopaedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China
                [b ]Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
                [c ]Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
                [d ]Research Institute of Orthopaedics, Zhejiang University, 310009, Hangzhou, China
                [e ]Department of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China
                [f ]Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, 650-0047, Japan
                Author notes
                []Corresponding author. zhengyuanyi@ 123456sjtu.edu.cn
                [∗∗ ]Corresponding author. Department of Orthopaedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China. zhangweilook@ 123456zju.edu.cn
                [∗∗∗ ]Corresponding author. 981637680@ 123456qq.com
                [1]

                Weiduo Hou, Chenyi Ye, and Mo Chen contributed equally to this work.

                Article
                S2452-199X(21)00028-1
                10.1016/j.bioactmat.2021.01.016
                7848724
                33553826
                d6bb5e22-d7f5-4016-a623-d799e523eb14
                © 2021 [The Author/The Authors]

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 November 2020
                : 18 December 2020
                : 12 January 2021
                Categories
                Article

                reactive oxygen species,prussian blue nanozyme,arthritis,inflammation,chondrocytes

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