Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating β-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway

He, Guanping; Nie, Jing‐Jun; Liu, Xiao; Ding, Zihao; Luo, Peng; Liu, Yu; Zhang, Bo-Wen; Wang, Renxian; Liu, Xiaoguang; Hai, Yong; Chen, Dafu

doi:10.1016/j.bioactmat.2022.05.006

Cited by 44 publications

(40 citation statements)

References 37 publications

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“…Is the difference in FLSs survival mediated by autophagy at 21%, 2% and 0.5% O 2 ? The results showed that 2% O 2 promoted the occurrence of autophagy, which con rmed that autophagy was one of the protective mechanisms of the body, consistent with the previous research results [27][28]. Autophagy increased at 0.5% O 2 , but signi cantly less than that at 2%O 2 .…”

Section: Discussionsupporting

confidence: 90%

Geniposide Augments Apoptosis in Fibroblast-like Synoviocytes by restoring Hypoxia-enhanced JNK-BNIP3-mediated Autophagy

Deng

Wang

et al. 2022

Preprint

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Objective As the main effector cells of chronic inflammation and hyperplasia of synovium, fibroblast-like synoviocytes (FLSs) show abnormal proliferation and insufficient apoptosis in hypoxic microenvironment, which is due to the increase of BNIP3-mediated autophagy. This study aimed to explore the mechanism of geniposide (GE) on hypoxia-induced hyper-proliferative FLSs with a focus on autophagy and JNK-BNIP3 pathway. Materials and methods The dynamic changes of autophagy and apoptosis and the expression of hypoxia related proteins in adjuvant arthritis (AA) rats were detected by immunohistochemistry and Western blot. The proliferation, autophagy, apoptosis and mitochondrial state of FLSs were detected by CCK-8, flow cytometry, immunofluorescence and transmission electron microscopy, respectively. Results The excessive accumulation of BNIP3 in synovium of AA rats was accompanied by inhibition of apoptosis and increase of autophagy. GE inhibited the expression of BNIP3, enhanced apoptosis and decreased autophagy, and improved chronic inflammation and hyperplasia of synovium. The amount of autophagy under different oxygen concentrations was the key to mediate the different survival rates of FLSs, and the inhibition of autophagy triggered apoptosis. GE suppresssed the proliferation of FLSs, and down-regulated autophagy, leading to the accumulation of ROS and the decrease of mitochondrial membrane potential (MMP), induced the increase of apoptosis, and suppressed the accumulation of BNIP3 and the hyperphosphorylation of JNK. Conclusions GE inhibited autophagy by restoring the hypoxia-induced activated JNK-BNIP3 pathway, inducing mitochondrial oxidative damage, augmented apoptosis and decreased survival rate of FLSs.

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Section: Discussionsupporting

confidence: 90%

Geniposide Augments Apoptosis in Fibroblast-like Synoviocytes by restoring Hypoxia-enhanced JNK-BNIP3-mediated Autophagy

Deng

Wang

et al. 2022

Preprint

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“…It is crucial to explore therapeutic strategies that can effectively inhibit OS cell metastasis. It was found that Zn 2+ released from ZnO NPs induced the degradation of β-catenin through the HIF-1α/BNIP3/LC3B-mediated mitophagy degradation pathway, thereby activating the HIF-1 and Wnt pathways to inhibit OS cell metastasis [ 162 ]. In addition, drug resistance is also an important reason that hinders the further improvement of the 5-year survival rate of OS patients [ 163 ].…”

Section: Mitophagy and Osteosarcomamentioning

confidence: 99%

Mitophagy—A New Target of Bone Disease

et al. 2022

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Bone diseases are usually caused by abnormal metabolism and death of cells in bones, including osteoblasts, osteoclasts, osteocytes, chondrocytes, and bone marrow mesenchymal stem cells. Mitochondrial dysfunction, as an important cause of abnormal cell metabolism, is widely involved in the occurrence and progression of multiple bone diseases, including osteoarthritis, intervertebral disc degeneration, osteoporosis, and osteosarcoma. As selective mitochondrial autophagy for damaged or dysfunctional mitochondria, mitophagy is closely related to mitochondrial quality control and homeostasis. Accumulating evidence suggests that mitophagy plays an important regulatory role in bone disease, indicating that regulating the level of mitophagy may be a new strategy for bone-related diseases. Therefore, by reviewing the relevant literature in recent years, this paper reviews the potential mechanism of mitophagy in bone-related diseases, including osteoarthritis, intervertebral disc degeneration, osteoporosis, and osteosarcoma, to provide a theoretical basis for the related research of mitophagy in bone diseases.

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“…DTCs that survive may grow immediately or enter a dormant state that may last for years, and they can be reactivated at any point in time to create an overt metastasis [ 66 ]. The primary tumor secretes different factors—such as CCL2, IL6, lysyl oxidase (LOX) and DKK1—into the circulation to create a pre-metastatic niche in the bone by altering the bone microenvironment [ 67 ]. Chemoattractive and adhesion molecules play important roles in the selective homing and retention of cancer cells in the bone marrow vasculature, such as stromal cell-derived factor-1 (SDF-1), a chemokine ligand that binds to CXC chemokine receptors 4 and 7 (CXCR4 and CXCR7).…”

Section: Bone Metastasismentioning

confidence: 99%

“…Based on the finding that CXCL12 expression inhibits cancer cell proliferation, instead maintaining them in a dormant state, Wang et al suggested that for the development of bone metastasis outgrowth, long-term survival, bone retention and dormancy are needed [ 63 ]. Other factors that were found to induce cancer cell dormancy are bone morphogenetic proteins (BMPs), TGFβ2 and growth-arrest-specific protein 6 (GAS6), factors that are also known to regulate HSC quiescence [ 67 ]. In a process that is not yet fully understood, dormant cells may be reactivated, after which they can initiate metastatic outgrowth in the bone microenvironment.…”

Section: Bone Metastasismentioning

confidence: 99%

Wnt Signaling in the Development of Bone Metastasis

Ben-Ghedalia-Peled

Vago

2022

Cells

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Wnt signaling occurs through evolutionarily conserved pathways that affect cellular proliferation and fate decisions during development and tissue maintenance. Alterations in these highly regulated pathways, however, play pivotal roles in various malignancies, promoting cancer initiation, growth and metastasis and the development of drug resistance. The ability of cancer cells to metastasize is the primary cause of cancer mortality. Bone is one of the most frequent sites of metastases that generally arise from breast, prostate, lung, melanoma or kidney cancer. Upon their arrival to the bone, cancer cells can enter a long-term dormancy period, from which they can be reactivated, but can rarely be cured. The activation of Wnt signaling during the bone metastasis process was found to enhance proliferation, induce the epithelial-to-mesenchymal transition, promote the modulation of the extracellular matrix, enhance angiogenesis and immune tolerance and metastasize and thrive in the bone. Due to the complexity of Wnt pathways and of the landscape of this mineralized tissue, Wnt function during metastatic progression within bone is not yet fully understood. Therefore, we believe that a better understanding of these pathways and their roles in the development of bone metastasis could improve our understanding of the disease and may constitute fertile ground for potential therapeutics.

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Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulating β-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway

Cited by 44 publications

References 37 publications

Geniposide Augments Apoptosis in Fibroblast-like Synoviocytes by restoring Hypoxia-enhanced JNK-BNIP3-mediated Autophagy

Geniposide Augments Apoptosis in Fibroblast-like Synoviocytes by restoring Hypoxia-enhanced JNK-BNIP3-mediated Autophagy

Mitophagy—A New Target of Bone Disease

Wnt Signaling in the Development of Bone Metastasis

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